StudyFinder
Search Results
221 Study Matches
Testing Low Dose Tamoxifen for Invasive Breast Cancer, the (LoTam) Trial (LoTam)
Jack Beranek - breastprotocols@alliancenctn.org
ALL
18 years and over
PHASE3
NCT06671912
Inclusion Criteria:
* Unilateral invasive adenocarcinoma of the breast that is histologically confirmed
* Invasive breast cancer is estrogen receptor positive in ≥ 10% of cells
* HER2 negative by current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
* The patient must have a multigene assay with a low-risk score, including any of the following (if more than one genomic assay was obtained, both are required to be low-risk):
* Oncotype DX recurrence score ≤ 25
* Mamma Print low risk
* Prosigna risk of recurrence ≤ 40
* Tumor size must be ≤ 3 cm by pathologic evaluation
* Adequate surgical removal of all clinically evident disease in the breast with either breast conserving surgery or mastectomy. Negative margins on final pathology are required. Additional excisions may be performed to obtain clear margins before registration
* No clinical (cN1, cN2, cN3) or pathologic (pN1mi, pN1, pN2, or pN3) evidence of lymph node involvement on either needle biopsy or surgical lymph node assessment. Patients with pN0(i+) or pN0 (mol+) are eligible
* Surgical axillary staging (sentinel lymph node biopsy ± axillary lymph node dissection) is completed according to physician discretion
* For patients with negative preoperative axillary ultrasonography, clinicians may selectively choose to forego surgical axillary staging. Ipsilateral axillary ultrasound showing no lymph node involvement with no evidence of lymphadenopathy or suspicious thickening is required in this scenario
* No pathological tumor size \> 3 cm or pT4
* No definitive clinical or radiologic evidence of metastatic disease
* No palpable or radiographically suspicious axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histologic confirmation that these lymph nodes are negative for tumor
* No suspicious microcalcifications, densities, or palpable abnormalities in the ipsilateral or contralateral breast, unless biopsied and found to be benign
* An interval of no more than 20 weeks between the date of surgery and the date of registration
* Must have had a bilateral mammogram or MRI within 6 months prior to registration
* Must be intending to take endocrine therapy for at least 5 years duration
* No prior treatment with endocrine therapy or chemotherapy for the currently diagnosed breast cancer prior to registration. (Short course endocrine therapy of ≤ 6 weeks duration is acceptable after core biopsy and before surgery, if genomic testing is assessed on the biopsy core and meets eligibility requirements for a low-risk score.)
* No use of oral hormone replacement therapy within 7 days prior to registration
* Age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Postmenopausal status confirmed as:
* No spontaneous menses ≥ 1 year
* No menses for \< 1 year with follicle stimulating hormone (FSH) and estradiol levels within a postmenopausal range according to institutional standards
* Previous bilateral surgical oophorectomy
* None of the following conditions:
* Abnormal or dysfunctional uterine bleeding within 1 year prior to study enrollment
* Any patient with known atypia or endometrial pathology that the opinion of the treating investigator would place the patient at undue risk of endometrial cancer with tamoxifen.
* Any patient with a known hypercoagulable state that in the opinion of the treating investigator would put the patient at undue risk of venous thromboembolism with tamoxifen
* No history of breast or thoracic radiotherapy for any previous condition. Patients may complete radiotherapy for the currently diagnosed breast cancer prior to registering for the study. In this scenario, registration must be completed within 12 weeks of completing breast radiotherapy
* No previous history of ipsilateral invasive breast cancer or ipsilateral ductal carcinoma in situ (DCIS), regardless of the disease-free interval
* No synchronous or previous contralateral invasive or non-invasive breast cancer
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* No patients with premenopausal status
* No current treatment with any endocrine therapy for breast cancer prevention or osteoporosis, including raloxifene, tamoxifen, or other selective estrogen receptor modulator. Patients intending to continue oral hormone replacement are not eligible
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial DRUG: Anastrozole, DRUG: Letrozole, DRUG: Exemestane, DRUG: Tamoxifen, PROCEDURE: Mammogram, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Dual X-ray Absorptiometry, PROCEDURE: Biospecimen Collection, OTHER: Questionnaire Administration
Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage 1 Breast Cancer AJCC v8, Anatomic Stage IIA Breast Cancer AJCC v8, Estrogen Receptor-Positive Breast Carcinoma, HER2-Negative Breast Carcinoma
A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)
IRB@prismahealth.org
ALL
1 year to 30 years old
PHASE2
NCT04546399
Inclusion Criteria:
* Patients must be \>= 1 and \< 31 years at time of enrollment
* Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories:
* Isolated bone marrow relapse
* Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
* Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes
* Patients with Down syndrome (DS) are eligible in the following categories:
* Isolated bone marrow relapse
* Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Of note, for patients with developmental delay (e.g., Down syndrome) regardless of age, Lansky scale may be substituted for Karnofsky scale. However, the requirement for ECOG 0-2 remains, regardless of known history of developmental delay
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Patients with prior blinatumomab or CD19+ chimeric antigen receptor therapy in the upfront setting will be eligible, provided relapsed lymphoblasts retain CD19 expression
* Patients must not have had a prior hematopoietic stem cell transplant
* A single intrathecal chemotherapy at the time of relapse will be allowed. If \< 7 days have elapsed between this intrathecal therapy (IT) and the start of protocol therapy, then the day 1 intrathecal chemotherapy (i.e. methotrexate, cytarabine, or triple intrathecal) may be omitted
* In the 28 days prior to enrollment, up to five days of post-relapse, pre-enrollment therapy (steroids and/or hydroxyurea only) is permissible
* Patients with Down syndrome who received pre-enrollment therapy and have a white blood count (WBC) \>= 30,000/ul at the time of enrollment still must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no "washout" is required
* Patients with Down syndrome who received pre-enrollment therapy and have a WBC \< 30,000/ul at the time of enrollment must be given a 24 hour "washout" before starting immunotherapy
* Note: There is no waiting period or "washout" for patients who relapse while receiving upfront therapy
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (within 7 calendar days prior to enrollment):
* Age: Maximum serum creatinine (mg/dL)
* 1 to \< 2 years: 0.6 (male), 0.6 (female)
* 2 to \< 6 years: 0.8 (male), 0.8 (female)
* 6 to \< 10 years: 1 (male), 1 (female)
* 10 to \< 13 years: 1.2 (male), 1.2 (female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: 1.7 (male), 1.4 (female)
* The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC)
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by echocardiogram, cardiac magnetic resonance imaging (MRI) or radionuclide angiogram
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
* Patients with B-lymphoblastic lymphoma (B-LLy)
* Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia
* Patients with Philadelphia chromosome positive (Ph+) B-ALL
* Patients with mixed phenotype acute leukemia (MPAL)
* Patients with known Charcot-Marie-Tooth disease
* Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype
* Patients with active, uncontrolled infection defined as:
* Positive bacterial blood culture within 48 hours of study enrollment
* Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection if cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline.
* Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed if blood cultures are negative for \> 48 hours
* A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection
* Active viral or protozoal infection requiring IV treatment
* Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible.
* Patients with uncontrolled HIV, hepatitis B, or hepatitis C infection. Of note, patients with known human immunodeficiency virus (HIV) infection on effective anti-retroviral therapy with undetectable viral load for at least the last 6 months prior to enrollment are eligible. Similarly, hepatitis B and hepatitis C positive patients who have been treated and have no viral detectable burden are also eligible
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* Patients with an active known/suspected autoimmune disease are not eligible. However, patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Group 4 and patients with DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible
* Note: Group 3 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible if this is NOT the only site of relapsed disease
* Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. Patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of this study. Men with female partners of childbearing potential should use effective contraception during the duration of their treatment. The effect of blinatumomab on fertility has not been evaluated. Blinatumomab is not recommended for pregnant women or women of childbearing potential (WOCBP) not using contraception. Females of reproductive potential must use effective contraception during treatment and for at least 48 hours after the last dose of blinatumomab. Studies in animal models have shown that nivolumab can adversely impair pregnancy. Thus, nivolumab is expected to cause fetal harm during pregnancy. WOCBP receiving nivolumab must continue contraception for a period of at least 5 months after the last dose of nivolumab. It is unknown whether nivolumab is present in breast milk, thus breastfeeding should be discontinued while a patient is receiving nivolumab
* Lactating females are not eligible unless they agree to not breastfeed their infants. It is unknown whether blinatumomab or its metabolites are excreted in human breast milk. Women are not permitted to breastfeed while receiving blinatumomab and for the last 48 hours after the last blinatumomab dose. Due to the potential for serious adverse reactions in the breastfed infant, women are not permitted to breastfeed during treatment and for 5 months after the last nivolumab dose RADIATION: 3-Dimensional Conformal Radiation Therapy, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cytarabine, DRUG: Dexamethasone, DRUG: Hydrocortisone Sodium Succinate, PROCEDURE: Lumbar Puncture, DRUG: Mercaptopurine, DRUG: Methotrexate, BIOLOGICAL: Nivolumab, DRUG: Pegaspargase, DRUG: Pegcrisantaspase, DRUG: Vincristine Sulfate
Down Syndrome, Recurrent B Acute Lymphoblastic Leukemia
Study of Anti-CEACAM5 ADC M9140 in Participants With Advanced Solid Tumors (PROCEADE PanTumor)
Communication Center - service@emdgroup.com
ALL
18 years and over
PHASE1
NCT06710132
Inclusion Criteria:
* Participants are capable of signing informed consent as defined in protocol
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) below or equal to 1
* Participants with adequate hematologic, hepatic and renal function as defined in protocol
* Participant must have at least 1 lesion that is measurable using RECIST v1.1.
* Other protocol defined inclusion criteria could apply
Substudy GC:
* Participants in Part A and Part B with documented histopathological diagnosis of advanced or metastatic, HER2 negative, gastric or GEJ (with an epicenter 2 centimeter (cm) proximal or distal to the GEJ) adenocarcinoma, who were intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage that must have included (provided there is no medical contraindication and these agents are locally approved and available) a fluoropyrimidine and a platinum agent and an Immune checkpoint inhibitors (ICI) for participants with a known microsatellite instability-high (MSI-H) status or participants whose tumor express PD-L1 with a CPS greater than or equal (\>=) 1
* Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2
* Participants in Part A with CEACAM5high GC/GEJC (defined as IHC \>= 2+ staining in \>= 50% of tumor cells)
* Participants in Part B with CEACAM5low GC/GEJC (defined as IHC \>= 2+ staining in less than (\<) 50% of tumor cells)
* Other protocol defined inclusion criteria could apply
Substudy NSCLC:
* Participants in Part A and Part B with histologically or cytologically documented advanced (Stage III not eligible for resection or curative radiation) or metastatic NSCLC with or without driver genomic alterations
* Participants must have been intolerant/refractory to or progressed after systemic therapies for the advanced/metastatic stage
* Participants must have received and progressed (according to RECIST 1.1) on at least 1 line of therapy for the treatment of advanced/metastatic disease but no more than 3
* Participants who received a platinum-containing regimen or a targeted therapy as (neo)-adjuvant therapy for early-stage disease, if relapse or metastases occurred during or within 3 months after regimen completion, are considered to have received a line of treatment in the advanced setting
* Participants in Part A with CEACAM5 high-expressing EGFR tumors (including participants with any driver genomic alterations other than EGFR mutations
* Participants in Part B with CEACAM5 high known EGFR mutated tumors as assessed according to local clinical practice
* Other protocol defined inclusion criteria could apply
Substudy PDAC:
* Participants with histologically or cytologically confirmed advanced or metastatic PDAC, who were intolerant/refractory to or progressed after systemic therapies for the advanced metastatic stage that must have included (provided there is no medical contraindications, and these agents are locally approved and available; FOLFIRINOX regimen or NALIRIFNOX regimen or Nab-paclitaxel/gemcitabine regimen
* Participants must have received and progressed (according to RECIST 1.1) on at least one 1 line of therapy for the treatment of advanced/metastatic disease but no more than 2
* All participants will be screened using an IHC test to define CEACAM5 expression. Only participants with CEACAM5high expressing tumors will be eligible
* Other protocol defined inclusion criteria could apply
Exclusion Criteria:
* Participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years)
* Participants with known brain metastases, except those meeting the following criteria: Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Participants with diarrhea (liquid stool) or ileus Grade \> 1
* Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or bowel obstruction
* Cardiac arrhythmia, unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] \>= II) or a coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of \> 470 milliseconds (ms)
* Cerebrovascular accident/stroke (\< 6 months prior to enrollment)
* Other protocol defined exclusion criteria could apply
Substudy GC - Participants with prior therapy with irinotecan
Substudy NSCLC:
\- Participants with prior therapy with irinotecan
Substudy PDAC: none DRUG: M9140
Solid Tumors, Gastric Cancer, Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma (PDAC)
ADC, TOP1 inhibitor, Gastric Cancer, Gastroesophageal junction cancer, Non-Small Cell Lung Cancer, Pancreatic Cancer, Solid Tumors
No Opioids vs. Minimal Opioids Following Inguinal Hernia Repair
Study Coordinator - Abby.Birrell@PrismaHealth.org
ALL
18 years and over
PHASE4
NCT05929937
Inclusion Criteria:
* Adult patients aged 18 years or older
* Patients undergoing elective unilateral or bilateral inguinal hernia repairs
* Patients able to tolerate general anesthesia
Exclusion Criteria:
* Patients who cannot tolerate general anesthesia,
* Patients who cannot tolerate opioids or NSAIDS,
* Patients on opioids for chronic pain management (defined as near daily use within 90 days),
* Patients who undergo surgeries requiring extensive dissection/hernia sac reduction, or additional procedures,
* Patients requiring inpatient admission postoperatively
* Patients who are not able to understand and sign a written consent form DRUG: Opioids, OTHER: No opioids
Postoperative Pain, Inguinal Hernia
52 Week Study of Safety, PK, & Efficacy of XYOSTED® for Testosterone Replacement in Male Adolescents With Hypogonadism
Director Clinical Operations, MPH, CPM - jbitsura@halozyme.com
MALE
12 years to 17 years old
PHASE3
NCT06689085
Inclusion Criteria:
• Diagnosed with a deficiency or absence of endogenous testosterone due to primary or secondary hypogonadism of a known etiology. Children with combined hormone deficiencies are permitted to enroll (but the child must already be receiving treatment for concomitant hormonal deficiencies)
• Participants receiving prior testosterone treatment must be receiving a stable dose for at least 12 weeks prior to Screening
• Have parent(s) or a legal guardian who will voluntarily provide written informed consent for the child to participate in the study
• Willing to provide assent for participation in the study
• Be a male 12 to \< 18 years of age at the time of consent/assent
• Have Legally Authorized Representative who is able to understand and comply with all study procedures and agrees to have the child participate in the study program as outlined in the protocol
• Requires chronic pharmacologic support for the initiation and/or continuation of pubertal maturation
• Have a body mass index (BMI)-for-age greater than the 5th percentile and weigh ≥ 40 kg
• If sexually active with a female partner of child-bearing potential, agrees to:
• Practice true abstinence including 30 days after the last IP administration, or,
• Use 2 adequate forms of highly effective contraception, one of which should be a physical barrier, during the study and for 30 days after the last IP administration.
Exclusion Criteria:
• Has abnormal thyroid function tests at Screening
• Has suspected or known constitutional growth delay in growth and puberty (CDGP)
• Has evidence of possible nutritional or gastrointestinal disorder that may impact growth (e.g., abrupt weight loss within the 3 months prior to Screening, unmanaged celiac disease, inflammatory bowel disease)
• Has a known allergy or hypersensitivity to XYOSTED, or to any of its ingredients (testosterone enanthate and sesame oil)
• Participants receiving prior treatment with testosterone who are not on a stable dose for at least 12 weeks prior to Screening.
• Is receiving testosterone through a transdermal patch or gel in the 12 weeks prior to Screening.
• Has an allergy to foods or products containing sesame seeds or sesame oil
• Has Stage 1 hypertension, defined as the average of 2 or more seated right arm BP measurements exceeding the 95th percentile for age, sex, and height, or SBP ≥ 130 mm Hg and/or DBP ≥ 80 mm Hg (Flynn et al., 2017, in Appendix B), at Screening or Day 1.
• Has a clinically significant abnormal clinical laboratory test value at Screening, as determined by the Investigator including hematocrit ≥ 48%
• Has a history of deep venous thrombosis or pulmonary embolism
• Has evidence of a clinically significant 12-lead electrocardiogram (ECG) abnormality at Screening, as determined by the Investigator
• Has a current suspected or diagnosed (and unresected) tumor of the pituitary gland with the exception of Rathke's cleft cyst or a stable non-functioning pituitary microadenoma (ie, lesion size \< 10 mm that has not increased in size over a period of 1 year on repeat imaging), as determined by the Investigator
• Has an active malignancy or has received treatment for a malignancy within the 12 months before Screening
• Is currently receiving antipsychotic and/or selective serotonin reuptake inhibitor (SSRI) medications
• Is receiving any other medication or has a condition that would preclude safe participation in the study or confound the evaluation of safety, as determined by the Investigator
• Has a history of suicidal behavior (i.e., actions intended to harm oneself), suicidal ideation (ie, thoughts and plans about suicide), or suicide attempts
• Has affirmative responses on the Columbia Suicide Severity Rating Scale (C-SSRS) questionnaire
• Is currently taking supraphysiologic doses of systemic glucocorticoids for more than 3 weeks, except for intermittent short courses of exogenous glucocorticoids as needed for the treatment of asthma
• Has received any other investigational compound within 1 month prior to screening or 5 half-lives of the investigational product (whichever is longer)
• Has received gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors, androgens (eg, dehydroepiandrosterone \[DHEA\]), anabolic steroids such as oxandrolone, or other sex steroids within 12 months before the Screening visit, or would require these treatments at any time during the study.
• Receiving cytochrome P450 (CYP) 3A4 or P glycoprotein (P-gp) inhibitors/inducers or medications that are metabolized by CYP3A4 or P-gp within 30 days of enrolment.
• Has a history of alcohol or drug abuse
• Has a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other conditions that would preclude participation in the study, as determined by the Investigator
• Has chronic urticaria or dermatographism
• Has 25-hydroxy-vitamin D blood level \< 20 ng/mL. Participants with initial vitamin D blood measurement \< 20 ng/mL may receive supplementation per clinical practice during Screening and be rescreened up to 2 times
COMBINATION_PRODUCT: Testosterone enanthate
Hypogonadism, Male
primary hypogonadism, secondary hypogonadism
A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
Site Public Contact - Kim.Williams3@prismahealth.org
ALL
366 days to 46 years old
PHASE3
NCT06124157
Inclusion Criteria:
* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
Exclusion Criteria:
* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome (trisomy 21)
* Pregnancy and breast feeding
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Daunorubicin, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Imatinib, DRUG: Leucovorin, DRUG: Mercaptopurine, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Pegaspargase, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine
B Acute Lymphoblastic Leukemia
Fluid Management of Acute Decompensated Heart Failure Subjects Treated With Reprieve System (FASTR-II) (IDE-G210258) (FASTR-II)
Annemarie Forrest - aforrest@reprievecardio.com
ALL
22 years and over
PHASE3
NCT06898515
Inclusion Criteria:
• Diagnosis of HF with expected hospitalization \>24 hours, with \>1 new or worsening symptom and \>2 physical examination, laboratory, or invasive findings of HF, and receiving or with plans to receive a HF-specific treatment
• ≥10 lb. (4.5 kg) above dry weight as estimated by health care provider.
• Current outpatient prescription for daily loop diuretic.
• Participants ≥ 22 years of age able to provide informed consent and comply with study procedures.
• Elevated risk of diuretic resistance, as indicated by at least one of the following: Baseline hypochloremia OR Urine output \<1L in the 6 hours following IV loop diuretic \>=40 mg furosemide equivalent OR Spot urine sodium \<100 mmol/L 1-2 hours after IV loop diuretic \>= 40 mg furosemide equivalent
Exclusion Criteria:
• Urologic issues that would predispose the participant to a high rate of urogenital trauma or infection with catheter placement or known inability to place a Foley catheter.
• Hemodynamic instability as defined by any of the following: sustained systolic blood pressure \<90 mmHg for \>15 minutes within the past 48 hours, use of IV vasopressors or inotropes within past 48 hours, and/or current or previous mechanical circulatory support within the last week.
• Uncontrolled arrhythmias defined as sustained HR \>130 beats/min for \>10 minutes within the past 48 hours.
• Severe lung disease with chronic home oxygen requirement \>2L/min.
• Acute infection with evidence of systemic involvement (e.g., clinically suspected infection with fever or elevated serum white blood cell count).
• Estimated glomerular filtration rate (eGFR) \<25 ml/min/1.73m2 (calculated with either MDRD or CKD-EPI) or current use of renal replacement therapy (RRT).
• Significant left ventricular outflow obstruction, severe uncorrected complex congenital heart disease, known severe stenotic valvular disease, severe infiltrative or constrictive cardiomyopathy or other diagnosis that would make aggressive decongestion unsafe.
• Current or recent (\< 30 days) type I myocardial infarction (e.g., acute coronary syndrome such as NSTEMI or STEMI from plaque rupture), coronary artery bypass surgery, or stroke. An isolated troponin elevation (e.g., from volume overload or demand ischemia) is not a reason for exclusion.
• Severe electrolyte abnormalities (e.g., serum potassium \<3.0 mEq/L, magnesium \<1.3 mEq/L or sodium \<125 mEq/L). Note: These are based on baseline/screening labs. Participants whose electrolyte levels are repleted cannot be reassessed for inclusion in the trial.
• Other concomitant disease or condition the investigator believes will make it difficult to follow instructions or comply with study procedures and/or follow-up visits, including expected prolonged hospitalization for reasons other than decongestive therapy
• Currently enrolled in an interventional trial (observational studies are permitted).
• Life expectancy less than 6 months.
• Women who are pregnant or breastfeeding.
DEVICE: Reprieve System, DRUG: furosemide infusion
Acute Decompensated Heart Failure
A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma
Site Public Contact - Kim.Williams3@prismahealth.org
ALL
Up to 40 years old
PHASE2
NCT05691478
Inclusion Criteria:
* Patients must be \< 40 years of age at the time of enrollment.
* Patients must have a body surface area of \>= 0.8 m\^2 at the time of enrollment.
* Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies.
* Feasibility Phase (NOTE: as of Amendment #2B, the feasibility phase has been completed) Patients must have metastatic disease and a resectable primary tumor. Designation of a primary tumor as resectable will be determined at the time of diagnosis by the institutional multidisciplinary team.
For this study, metastatic disease is defined as one or more of the following:
* Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases.
* Lung metastases: defined as biopsy-proven metastasis or the presence of one or more pulmonary lesions \>= 5 mm, OR multiple pulmonary lesions \>= 3 mm or greater in size.
* Bone metastases: Areas suspicious for bone metastasis based on fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET) scan (or whole body technetium-99 bone scan if 18F-FDG-PET is unavailable at the treating institution) require confirmatory biopsy or supportive anatomic imaging of at least one suspicious site with either magnetic resonance imaging (MRI) or computed tomography (CT) (whole body 18F-FDG-PET/CT or 18F-FDG-PET/MR scans are acceptable).
* Efficacy Phases (Phase 2/3) NOTE: as of Amendment #2B, the efficacy phase is open for enrollment.
Patients with both localized and metastatic disease are eligible for the efficacy phase, regardless of resectability. Patients will be enrolled to two separate cohorts:
* Cohort 1 (Standard Risk): Patients with non-pelvic primary osteosarcoma deemed to be resectable at the time of diagnosis by the institutional multidisciplinary team, without evidence of metastatic lesions.
* Cohort 2 (High-Risk): Patients with a primary pelvic tumor, a primary tumor designated as unresectable by the institutional multidisciplinary team, AND/OR radiographic evidence of metastatic lesions.
* A serum creatinine based on age/sex as follows (within 7 days prior to enrollment unless otherwise indicated):
* (Age: Maximum Serum Creatinine \[mg/dL\]; Sex)
* 1 month to \< 6 months: 0.4 (male); 0.4 (female)
* 6 months to \< 1 year: 0.5 (male); 0.5 (female)
* 1 to \< 2 years: 0.6 (male); 0.6 (female)
* 2 to \< 6 years: 0.8 (male); 0.8 (female)
* 6 to \< 10 years: 1 (male); 1 (female)
* 10 to \< 13 years: 1.2 (male); 1.2 (female)
* 13 to \< 16 years: 1.5 (male); 1.4 (female)
* \>= 16 years: 1.7 (male); 1.4 (female)
* OR - a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2
* OR - a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard).
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility.
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment unless otherwise indicated)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (within 7 days prior to enrollment unless otherwise indicated)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* No history of congenital prolonged corrected QT (QTc) syndrome, New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias
* Shortening fraction of \>= 27%, or
* Ejection fraction of \>= 50%
* Corrected QT interval by Fridericia (QTcF) \< 480 msec on electrocardiogram. Patients with Grade 1 prolonged QTc (450-480 msec) at time of study enrollment should have correctable causes of prolonged QTc addressed if possible (i.e., electrolytes, medications).
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment unless otherwise indicated)
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment) (within 7 days prior to enrollment unless otherwise indicated)
* Hemoglobin \>= 8.0 g/dL (within 7 days prior to enrollment unless otherwise indicated)
* International normalized ratio (INR) =\< 1.5 (within 7 days prior to enrollment unless otherwise indicated)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4, CYP2D6, and/or MRP2 transporter protein.
* All patients and/or their parents or legal guardians must sign a written informed consent.
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
* Patients who have received previous systemic therapy for osteosarcoma or a prior oncologic diagnosis.
* Patients who have central nervous system metastases.
* Patients with central cavitating pulmonary lesions invading or encasing any major blood vessels in the lung.
* Patients who are unable to swallow tablets. Tablets cannot be crushed or chewed.
* Patients with gastrointestinal disorders including active disorders associated with a high risk of perforation or fistula formation. Specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, bowel obstruction, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
* Patients with active bleeding or bleeding diathesis. No clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding within 3 months prior to enrollment.
* Patients with uncompensated or symptomatic hypothyroidism. Patients who have hypothyroidism controlled with thyroid replacement hormone are eligible.
* Patients with moderate to severe hepatic impairment (Child-Pugh B or C).
* Patients who have had primary tumor resection or attempted curative resection of metastases prior to enrollment.
* Patients who have undergone other major surgical procedure (eg, laparotomy) within 14 days prior to enrollment. Thoracoscopic procedures for diagnostic purposes (biopsy of lung nodule) and central access such as port-a-cath placement are allowed.
* Patients with a history of serious or non-healing wound or bone fracture (pathologic fracture of primary tumor is not considered exclusion).
* Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of cabozantinib.
* Patients with previously identify allergy or hypersensitivity to components of the study treatment formulations.
* Patients who are receiving any other investigational agent not defined within this protocol are not eligible.
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
* Patients who received enzyme-inducing anticonvulsants within 14 days prior to enrollment.
* Patients with a prior history of hypertension (\> 95th percentile for age, height, and sex for patients \< 18 years and \> 140/90 mmHg for patients \>= 18 years requiring medication for blood pressure control.
* Patients who are receiving drugs that prolong QTc.
* Patients receiving anticoagulation with oral coumarin agents (eg warfarin), direct thrombin inhibitors (eg dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (eg, clopidogrel). Low dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH and direct factor Xa inhibitors rivaroxaban or apixaban are allowed in subjects who are on a stable dose for at least 6 weeks before the first dose of study treatment, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
* Patients receiving strong CYP3A4 inducers or strong CYP3A4 inhibitors.
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
* Lactating females who plan to breastfeed their infants.
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of protocol therapy. PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Doxorubicin Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, PROCEDURE: Surgical Procedure, PROCEDURE: X-Ray Imaging
High Grade Osteosarcoma, Localized Osteosarcoma, Metastatic Osteosarcoma, Secondary Osteosarcoma
Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial
Site Public Contact - Kim.Williams3@prismahealth.org
ALL
18 years and over
PHASE3
NCT06498635
Inclusion Criteria:
* Participants must have histologically or cytological confirmed diagnosis of clinical stage II-IIIB (excluding clinical N3 disease) non-small cell lung cancer (NSCLC)
* Participants must have had a complete (R0) resection of NSCLC (with appropriate lymph node sampling as defined by the National Comprehensive Cancer Network \[NCCN\] guidelines) within 84 days (12 weeks) prior to randomization. Acceptable types of surgical resection are: lobectomy, sleeve resection, bi-lobectomy, or pneumonectomy. Wedge resection is not allowed.
* Note the NCCN guidelines: N1 and N2 node resection and mapping is a routine component of lung cancer resections. It is recommended at a minimum one N1 and three N2 stations is sampled or complete lymph node dissection. Formal ipsilateral mediastinal lymph node dissection is indicated for participants undergoing resection for N2 disease
* Participants must have a pathologic complete response (pCR) (no viable tumor in the resected specimen or lymph nodes), as determined by local pathology review
* Participants must have a PD-L1 status result (e.g. \[\< 1% versus \>= 1% or unknown\])
* Participants must not have known EGFR mutations, or ALK gene fusion
* Participants must have received at least two cycles of neoadjuvant platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy. The neoadjuvant treatment must be Food and Drug Administration (FDA) approved and standard of care as listed in NCCN guidelines
* Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for NSCLC treatment while receiving treatment on this study
* Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 28 days prior to randomization
* Participants must not have medical contraindications or severe adverse events to receiving anti-PD-1 or anti-PD-L1 therapy
* Participants must not have received post-operative radiation therapy (PORT) for NSCLC
* Participants must not have any unresolved toxicity National Cancer Institute (NCI) CTCAE grade ≥ 2 from previous anticancer therapy with the exception of alopecia, and vitiligo. Note, participants with grade ≥2 neuropathy may be included at the discretion of the treating investigator. Note, participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the discretion of the treating investigator
* Participant must be ≥ 18 years old at time of study entry
* Participants must have body weight \> 30 kg
* Participant must have Zubrod performance status of 0-2
* Participant must have a complete medical history and physical exam within 28 days prior to randomization
* Hemoglobin \> 9.0 g/dL (within 28 days prior to randomization)
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin ≤ 1 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to randomization)
* Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × institutional ULN (within 28 days prior to randomization)
* Participants must have a calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to randomization. For creatinine clearance formula see the tools on the Clinical Research Associate (CRA) Workbench https://txwb.crab.org/TXWB/Tools.aspx
* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
* Participants with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization
* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated
* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated
* Participants must not have had an organ transplant
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participant must not have medical contraindications to receiving immunotherapy, including history of non-infectious pneumonitis that required steroids or active autoimmune disease that has required systemic treatment with disease modifying agents, corticosteroids or immunosuppressive drugs in the past two years. Replacement therapy (e.g. thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Intra-articular steroid injections are allowed
* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method during protocol therapy and for 6 months following completion of protocol therapy with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen. Participants should not breastfeed during protocol therapy and for 6 months following completion of protocol therapy
* Participants must not have received a live or live attenuated vaccine within 28 days prior randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever rabies, Bacillus Calmette-Guerin (BCG) and typhoid vaccine. Seasonal influenza vaccines and coronavirus disease 19 (COVID-19) vaccines are allowed, however, intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated, and are not allowed
* Participants must be offered the opportunity to participate in specimen banking
* Participants who can complete FACT-L, FACT-BRM, and PRO-CTCAE questionnaires forms in English, or Spanish must agree to participate in the patient-reported outcome study
* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, BIOLOGICAL: Durvalumab, OTHER: Patient Observation, OTHER: Questionnaire Administration
Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8
Study to Test OBI-3424 in Patients With T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LBL)
Site Public Contact - Kim.Williams3@prismahealth.org
ALL
12 years and over
PHASE1
NCT04315324
Inclusion Criteria:
* Patients must have a diagnosis of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) based on World Health Organization (WHO) classification. Patients with relapsed/refractory T-cell lymphoblastic lymphoma are eligible if lymphoblasts are \>= 5% in the bone marrow or in the peripheral blood by morphology or flow cytometry
* Patients must have evidence of acute leukemia in their peripheral blood or bone marrow. Patients must have \>= 5% lymphoblasts in the peripheral blood or bone marrow within 14 days prior to registration. Patients with only extramedullary disease are not eligible
* Patients ≥ 18 years of age must be refractory to or have relapsed following a standard induction chemotherapy. Patients \< 18 years of age must have relapsed or must be refractory after 2 or more chemotherapy cycles (example: induction and consolidation)
* A standard chemotherapy induction regimen is defined as any program of treatment that includes:
* Vincristine and corticosteroids plus at least one more chemotherapy agent
* Cytarabine and anthracycline, or
* High dose cytarabine (defined as at least 1 gr/m\^2 per individual dose unless adjustments were required for renal/liver function)
* Patients must have no evidence of central nervous system disease within 28 days prior to registration based on cerebrospinal fluid (CSF) studies. Patients with clinical signs or symptoms consistent with central nervous system (CNS) involvement must have a lumbar puncture which is negative for CNS involvement; the lumbar puncture must be completed within 28 days prior to registration. Patients with CNS1 or CNS2 are eligible; however patients with CNS3 are not eligible
* Note that the patients may receive intrathecal chemotherapy with the initial lumbar puncture. This may count as the first dose of intrathecal therapy required as part of the study
* Prior nelarabine therapy is not required. In addition, for patients ≥ 18 years of age who received nelarabine during initial induction or post-remission treatment are eligible only if the physician does not feel they would benefit from other, multi-agent chemotherapy
* Patients must not have had chemotherapy or investigational agents within 14 days prior to registration except for corticosteroids, oral 6-mercaptopurine, oral methotrexate, vincristine, intrathecal chemotherapy, or hydroxyurea. For participants who have received radiation therapy, at least 7 days must have elapsed from the end of radiation prior to registration and participants must not currently be experiencing toxicities from radiation therapy
* Patients must not have undergone allogeneic hematopoietic transplant within 90 days prior to registration
* Patients must have no evidence of active \>= grade 2 acute graft versus host disease (GVHD) or moderate or severe limited chronic GVHD. Patients must have no history of extensive GVHD of any severity within 90 days prior to registration. Patients who are post-transplant must be off calcineurin inhibitors for at least 21 days to be eligible. Extensive GVHD is defined as 1) generalized skin involvement or 2) localized skin involvement and/or hepatic dysfunction plus liver histology or cirrhosis or involvement of eye or minor salivary organ or oral mucosa or any other target organ
* Patients must be \>= 12 years of age
* Patients ≥ 16 years of age must have a Zubrod Performance Status of 0-3. Patients \< 16 years of age must have a Lansky score of ≥ 50
* Patients must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) within 14 days prior to registration
* Patients ≥ 18 years of age must have creatinine clearance \> 30 mL/min within 14 days prior to registration according to the Cockcroft Gault equation
* Patients 12-17 years of age must have adequate renal function within 14 days prior to registration defined as serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) according to age or a calculated estimated glomerular filtration rate (eGFR) (based on Schwartz formula) or radioisotope glomerular filtration rate (GFR) ≥ 50ml/min/1.73 m\^2
* Patients must have direct bilirubin =\< 1.5 x institutional upper limit of normal (ULN) within 14 days prior to registration
* Patients must have alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN) or =\< 5.0 x ULN (if thought to be related to leukemic involvement) within 14 days prior to registration
* Prothrombin time (PT)/partial thromboplastin time (PTT)/ fibrinogen (as clinically indicated for example but not limited to history of bleeding or active bleeding, concern for disseminated intravascular coagulation) (within 14 days prior to registration to obtain baseline measurements)
* From metabolic panel (comprehensive or basic): sodium, potassium, chloride, carbon dioxide (CO2), and blood urea nitrogen (BUN) (within 14 days prior to registration to obtain baseline measurements)
* Patients must be able to safely discontinue use of strong inhibitors/inducers of CYP3A4 or PgP-g-p and must be able to safely discontinue use of naproxen for 48 hours before and after each dose of OBI-3424
* Patients with known human immunodeficiency virus (HIV)-infection are eligible providing they are on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test within 6 months prior to registration. (HIV viral load testing is required only for patients with known HIV infection). Patients must not be receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4
* Patients with evidence of chronic hepatitis B virus (HBV) infection may be eligible provided that they have an undetectable HBV viral load within 28 days prior to registration. Patients may be currently receiving HBV treatment. (HBV viral load testing is required only for patients with known HBV infection). Patients must not be receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4
* Patients with known history of hepatitis C virus (HCV) infection may be eligible provided that they have an undetectable HCV viral load within in 28 days prior to registration. Patients may be currently receiving treatment. (HCV viral load testing is required only for patients with known HCV infection). Patients must not be receiving antiviral therapies that are known strong inhibitors or inducers of CYP3A4
* Patients must not have a known history of prolonged QT interval by Fridericia (QTcF) (interval \> 450 msec for males; \> 470 msec for females). Patients that had transient prolongation of QTc secondary to medications or electrolyte abnormalities are not excluded if the QTc normalized and remain within acceptable QTcF range (interval \> 450 msec for males; \> 470 msec for females). Additionally, suspected medications should be no longer required or used, and electrolyte abnormalities must have normalized
* Patients must not be pregnant or nursing due to the teratogenic potential of the drug used on this study. Females of reproductive potential must have a negative serum pregnancy test within 14 days prior to registration. Women/men of reproductive potential must have agreed to use an effective contraceptive method during and up to 6 months after treatment. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Patients must not have other active malignancies for which they have received treatments within 6 months prior to registration excluding localized malignancies that do not require systemic treatment
* Patients must agree to have bone marrow and blood specimens submitted for MRD testing
* Patients must be offered the opportunity to participate in specimen banking. With patient consent, residuals from specimens submitted will be retained and banked for future research
* Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with fedral, local, institutional and Central Institutional Review Board (CIRB) guidelines unless they are unable to provide consent based on age (\< 18 years) or based on impaired decision-making capabilities. For patients \< 18 years of age or with impaired decision making capabilities, parents or other legally authorized representatives must sign and give informed consent on behalf of study participants in accordance with applicable federal, local, institutional and CIRB regulations
* As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* This trial will use a slot reservation system to enroll the Phase I portion of the study. Patients planning to enroll at this phase of the study must first have a slot reserved in advance of the registration. All site staff will use OPEN to create a slot reservation DRUG: AKR1C3-activated Prodrug AST-3424, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Computed Tomography
Recurrent T Acute Lymphoblastic Leukemia, Refractory T Acute Lymphoblastic Leukemia, Refractory T Lymphoblastic Lymphoma, T Lymphoblastic Lymphoma
A Dose-Finding Study of Tebapivat to Assess Efficacy, and Safety in Participants With Sickle Cell Disease (SCD)
Agios Medical Affairs - medinfo@agios.com
ALL
16 years and over
PHASE2
NCT06924970
Key
Inclusion Criteria:
* Documented diagnosis of SCD (HbSS, HbSC \[combined heterozygosity for hemoglobins S and C\], sickle hemoglobin \[HbS\]/β0-thalassemia, HbS/β+-thalassemia, or other sickle cell syndrome variants).
* Hemoglobin ≥5.5 and ≤10.5 grams per decilitre (g/dL). Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the screening period.
* If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before randomization. Discontinuation of hydroxyurea requires a 90-day washout before providing informed consent.
Key Exclusion Criteria:
* Receiving regularly scheduled red blood cell (RBC) transfusion therapy (also termed chronic, prophylactic, or preventative transfusion); episodic transfusion in response to worsened anemia or vaso-occlusive crisis (VOC) is permitted. Additionally, a participant who requires episodic transfusion(s) may not have received a transfusion(s) within 60 days before providing informed consent or during the screening period.
* \>10 sickle cell pain crisis (SCPCs) in the 12 months before providing informed consent.
* Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥10 weeks before randomization.
* Hospitalized for an SCPC and/or other vaso-occlusive event within 14 days before providing informed consent or within 14 days before randomization. If an SCPC occurs during the screening period, the screening period may be extended with Medical Monitor approval.
* Receiving treatment with voxelotor, crizanlizumab, or L-glutamine within 90 days before randomization.
* Platelet count \ DRUG: Tebapivat, DRUG: Tebapivat Matched Placebo
Sickle Cell Disease