Venetoclax and Vincristine in Treating Patients With Relapsed or Refractory T-cell or B-cell Acute Lymphoblastic Leukemia
- Conditions
- Recurrent Adult Lymphoblastic LymphomaRecurrent B Acute Lymphoblastic LeukemiaRecurrent B Lymphoblastic LymphomaRecurrent T Acute Lymphoblastic LeukemiaRecurrent T Lymphoblastic LymphomaRefractory B Acute Lymphoblastic LeukemiaRefractory B Lymphoblastic LymphomaRefractory T Acute Lymphoblastic LeukemiaRefractory T Lymphoblastic Lymphoma
- Interventions
- Procedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Lumbar PunctureProcedure: Positron Emission Tomography
- Registration Number
- NCT03504644
- Lead Sponsor
- ECOG-ACRIN Cancer Research Group
- Brief Summary
This phase Ib/II trial studies the side effects and best dose of venetoclax and how well it works when given together with vincristine in treating patients with T-cell or B-cell acute lymphoblastic leukemia that has come back (recurrent) or does not respond to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as vincristine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax together with vincristine may work better in treating patients with acute lymphoblastic leukemia compared to vincristine alone.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose of venetoclax in combination with vincristine liposomal (liposomal vincristine)/vincristine sulfate in patients with relapsed or refractory T-cell and B-cell acute lymphoblastic leukemia (ALL). (Phase I) II. Safety assessment and toxicity characterization after treatment of venetoclax in combination with liposomal vincristine in patients with relapsed or refractory T-cell and B-cell ALL. (Phase I) III. To determine the preliminary efficacy of venetoclax in combination with liposomal vincristine/vincristine sulfate to induce complete remission (CR)+ incomplete complete remission (CRi) in patients with relapsed or refractory T-cell and B-cell ALL. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the progression free survival, overall survival and toxicity after the combination treatment in patients with relapsed or refractory T-cell and B-cell ALL. (Phase II) II. To determine the rate of minimal residual disease (MRD) negativity rate of the combination. (Phase II)
EXPLORATORY/CORRELATIVE OBJECTIVES:
I. To determine if genetic signature as determined by next generation sequencing can predict response to combination. (Phase II) II. To determine if immunophenotype of ALL is associated with response to combination. (Phase II) III. To determine if the BH3 profile is associated with response to combination. (Phase II) IV. To determine if relative expression of BCL-2 measure by flow cytometry is associated with response to combination. (Phase II)
OUTLINE: This is a phase Ib, dose-escalation study of venetoclax followed by a phase II study.
PHASE Ib: Patients receive venetoclax orally (PO) once daily (QD) on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal intravenously (IV) over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo computed tomography (CT) and/or positron emission tomography (PET) scan as well as a lumbar puncture as clinically indicated.
PHASE II: Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated.
After completion of study treatment, patients are followed up every 6 months for 5 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 74
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 0: Patient must be considered a potential candidate for the trial
- NOTE: Enrollment to Step 0 may occur prior to or following completion of the assessments to verify patient eligibility for Step 1 registration; bone marrow and/or peripheral blood specimens collected during Step 0 or prior to treatment on Step 1 must be submitted for central review in order for the patient to be considered evaluable; results will not be reported to the site and will not impact patient participation in the trial
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients must have a diagnosis of:
- Relapsed or refractory B-cell or T-cell ALL after multi-agent chemotherapy
- Patients with < 5% blasts may enroll on trial in phase I portion provided that minimal residual disease (MRD) is present at > 10^-3 as tested on an assay with minimum sensitivity of 10^-4 OR
- Relapsed lymphoblastic lymphoma
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C): Age >= 18 years
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Eastern Cooperative Oncology Group (ECOG) performance status 0-2
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Adequate liver function with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than 3 x upper limit of normal and total bilirubin less than 2 mg/dL within 10 days prior to first dose of study agent
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Circulating white blood cell (WBC) count must not be above 25 x 10^9/L at the time of registration
- Patients with WBC count above 25 x 10^9/L are eligible if they have started steroids or hydroxyurea per institutional guidelines
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Glomerular filtration rate (GFR) of at least 40 mL/min within 7 days prior to first dose of study agent
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: All patients of childbearing potential must have a blood test or urine study with a minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) within 2 weeks prior to registration to rule out pregnancy
- A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients must not expect to conceive or father children by using accepted and highly effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 30 days after the last dose of venetoclax
- Should a patient or a partner of a patient become pregnant or suspect they are pregnant while participating in the study, the treating physician should be notified immediately
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: No evidence of prior solid malignancy except adequately treated non-melanoma skin cancer, in situ cervical carcinoma, or any surgically- or radiation-cured malignancy continuously disease free for >= 2 years so as not to interfere with interpretation of radiographic response
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients may be enrolled with a prior allogeneic hematopoietic stem cell transplant (HSCT) but the transplant date must be at least 90 days before date of registration to step 1; patient must be off immunosuppression and without active graft versus host disease (GVHD) prior to registration to step 1 if previous HSCT
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 0: Patient must be considered a potential candidate for the trial
- NOTE: Enrollment to Step 0 may occur prior to or following completion of the assessments to verify patient eligibility for Step 1 registration
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Relapsed or refractory B-cell or T-cell ALL, including lymphoblastic lymphoma, after at least one line of chemotherapy
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Age >= 18 years
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: ECOG performance status 0-2
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Adequate liver function with AST/ALT less than 3 x upper limit of normal and total bilirubin less than 2 mg/dL within 10 days prior to first dose of study agent
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Circulating WBC count must not be above 25 x 10^9/L at the time of registration to step 1
- Patients with WBC count above 25 x 10^9/L are eligible if they have started steroids or hydroxyurea per institutional guidelines
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: GFR of at least 40 mL/min within 7 days prior to first dose of study agent
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: All patients of childbearing potential must have a blood test or urine study with a minimum sensitivity 25 IU/L or equivalent units of HCG within 2 weeks prior to registration to rule out pregnancy.
- A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not expect to conceive or father children by using accepted and highly effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 30 days after the last dose of venetoclax
- Should a patient or partner of a patient become pregnant or suspect she is pregnant while participating in this study, the treating physician should be informed immediately
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients may be enrolled with a prior allogeneic hematopoietic stem cell transplant (HSCT) but the transplant date must be at least 90 days before date of enrollment; patient must be off immunosuppression and without active GVHD prior to enrollment if previous HSCT. Low-dose steroids (10mg or less) are allowed
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients of childbearing potential must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients with isolated testicular or central nervous system (CNS) relapsed disease are not eligible
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients must not have Burkitt's lymphoma/leukemia based on the World Health Organization (WHO) criteria
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients must not have active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or the use of CNS-directed local treatment for active disease within the prior 28 days; prophylactic intrathecal chemotherapy is allowed; previously treated CNS disease with documented clearance of the CSF will be allowed
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients will not be enrolled if they received prior chemotherapy within 2 weeks before registration to step 1 with the following exceptions: to reduce the circulating lymphoblast count or palliation or for ALL maintenance (mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors)
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients cannot have poorly controlled chronic viral infections including hepatitis B, C, or human immunodeficiency virus (HIV); HIV positive patients are allowed on this study if they have a CD4 count >= 400, and are on a stable antiviral regimen
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients with New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia may not be enrolled
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients with serious medical or psychiatric illness that in the opinion of the primary investigator is likely to interfere with study participation may not be enrolled
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients must not be taking any other experimental medications within 21 days prior to registration. Clinical trial medications that are Food and Drug Administration (FDA) approved will be allowed within 14 days prior to registration
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients should not have received the following within 7 days prior to the first dose of study drug:
- Strong and moderate CYP3A inhibitors;
- Strong and moderate CYP3A inducers
-
ELIGIBILITY CRITERIA - PHASE I (ARMS A, B, C) - STEP 1: Patients must not have grade 3 or higher peripheral neuropathy or history of grade 3 or higher peripheral neuropathy. Patients with familial demyelinating disease like Charcot-Marie-Tooth disease are also excluded
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients with prior venetoclax treatment for ALL will be excluded
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not be pregnant or breast-feeding due to risk of fetal harm by the chemotherapeutic agents prescribed in this protocol
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: No evidence of prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical or breast carcinoma, or chemotherapy-surgically- or radiation-cured malignancy continuously disease free for >= 2 years
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients with isolated testicular or CNS relapsed disease are not eligible
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not have Burkitt's lymphoma/leukemia based on the WHO criteria
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not have active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or the use of CNS-directed local treatment for active disease within the prior 28 days; prophylactic intrathecal chemotherapy is allowed; previously treated CNS disease with documented clearance of the CSF will be allowed and once cleared, prophylactic intrathecal chemotherapy can be continued
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patient will not be enrolled if they received prior chemotherapy within 2 weeks before enrollment with the following exceptions: to reduce the circulating lymphoblast count or palliation (i.e., steroids or hydroxyurea), for ALL maintenance (mercaptopurine, methotrexate, vincristine, thioguanine, and/or tyrosine kinase inhibitors)
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients cannot have poorly controlled chronic viral infections including hepatitis B, C, or HIV; HIV positive patients with undetectable viral load are allowed
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients with NYHA class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia may not be enrolled
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients with serious medical or psychiatric illness that in the opinion of the primary investigator is likely to interfere with study participation may not be enrolled
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not be participating in any other clinical trial or taking any other experimental medications within 21 days prior to registration
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not have received the following within 7 days prior to the first dose of study drug or while on study treatment:
- Strong and moderate CYP3A inhibitors;
- Strong and moderate CYP3A inducers
-
ELIGIBILITY CRITERIA - PHASE II (ARM D) - STEP 1: Patients must not have grade 3 or higher peripheral neuropathy or history of grade 3 peripheral neuropathy; patients with familial demyelinating diseases like Charcot-Marie-Tooth disease also excluded
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase II (venetoclax, vincristine liposomal/sulfate) Vincristine Liposomal Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase II (venetoclax, vincristine liposomal/sulfate) Vincristine Sulfate Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase II (venetoclax, vincristine liposomal/sulfate) Lumbar Puncture Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase Ib (venetoclax, vincristine liposomal) Biospecimen Collection Patients receive venetoclax PO QD on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase Ib (venetoclax, vincristine liposomal) Computed Tomography Patients receive venetoclax PO QD on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase Ib (venetoclax, vincristine liposomal) Lumbar Puncture Patients receive venetoclax PO QD on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase Ib (venetoclax, vincristine liposomal) Positron Emission Tomography Patients receive venetoclax PO QD on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase Ib (venetoclax, vincristine liposomal) Venetoclax Patients receive venetoclax PO QD on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase Ib (venetoclax, vincristine liposomal) Vincristine Liposomal Patients receive venetoclax PO QD on days 1-42 of cycle 1 and days 43-70 of cycle 2. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks starting on day 15 of cycle 1. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase II (venetoclax, vincristine liposomal/sulfate) Biospecimen Collection Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase II (venetoclax, vincristine liposomal/sulfate) Computed Tomography Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase II (venetoclax, vincristine liposomal/sulfate) Positron Emission Tomography Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated. Phase II (venetoclax, vincristine liposomal/sulfate) Venetoclax Patients receive venetoclax PO QD on days 1-28 of each cycle. Patients also receive vincristine liposomal IV over 1 hour weekly for 4 weeks on day 1 of each cycle or vincristine sulfate IV weekly on days 1, 8, 15, and 22 of cycle 1 and once every 4 weeks on day 1 of each subsequent cycle. Cycles repeat every 28 days. Patients who achieve at least a stable disease response may continue treating at the discretion of the treating physician in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the trial. Patients may also undergo CT and/or PET scan as well as a lumbar puncture as clinically indicated.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of venetoclax (Phase I) Up to 70 days Will be determined by dose limiting toxicity. The phase I portion of this study will use a standard 3+3 design.
Incidence of toxicities (Phase I) Up to 5 years Toxicities will be assessed and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Complete remission (CR) + complete remission incomplete (CRi) rate (Phase II) Up to end of cycle 3 (1 cycle = 28 days) A 90% confidence interval will be computed.
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) (Phase II) From study registration to documented disease progression or death from any cause, whichever occurs first, assessed up to 5 years Will be estimated using the Kaplan-Meier method, and the median PFS along with its corresponding 95% confidence interval will be reported.
Overall survival (OS) (Phase II) From study registration to death from any cause, assessed up to 5 years Will be estimated using the Kaplan-Meier method, and the median OS along with its corresponding 95% confidence interval will be reported.
Incidence of toxicities (Phase II) Up to 5 years Toxicity incidences will be assessed and graded according to the CTCAE and will be tabulated by patient cohort.
Change in intracellular BCL-2 expression (Phase II) Baseline up to 5 years Will be assessed by flow cytometry and dichotomized into two groups by the median (low versus \[vs\] high). Univariate Cox proportional hazards (PH) models will be used to evaluate the association of the BCL-2 expression at baseline and immunophenotype (B-cell and T-cell acute lymphoblastic leukemia) with OS and PFS, separately. Logistic regression models will be used to investigate the association of the BCL-2 expression at baseline and immunophenotype with response (CR/CRi/partial remission \[PR\] vs others by 70 days). Multivariable Cox PH modelling and logistic regression modelling will also be used to adjust for the effect of covariates that are possibly associated with these efficacy outcomes.
Minimal residual disease (MRD) negativity rate (Phase II) Up to 5 years
Trial Locations
- Locations (170)
OSF Saint Francis Medical Center
🇺🇸Peoria, Illinois, United States
Illinois CancerCare-Peru
🇺🇸Peru, Illinois, United States
Valley Radiation Oncology
🇺🇸Peru, Illinois, United States
Illinois CancerCare-Princeton
🇺🇸Princeton, Illinois, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Springfield Clinic
🇺🇸Springfield, Illinois, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Illinois CancerCare - Washington
🇺🇸Washington, Illinois, United States
Central Care Cancer Center - Garden City
🇺🇸Garden City, Kansas, United States
Central Care Cancer Center - Great Bend
🇺🇸Great Bend, Kansas, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Minnesota Oncology - Burnsville
🇺🇸Burnsville, Minnesota, United States
Cambridge Medical Center
🇺🇸Cambridge, Minnesota, United States
Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Unity Hospital
🇺🇸Fridley, Minnesota, United States
Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Saint Luke's Cancer Institute - Meridian
🇺🇸Meridian, Idaho, United States
Saint Luke's Cancer Institute - Nampa
🇺🇸Nampa, Idaho, United States
Saint Luke's Cancer Institute - Twin Falls
🇺🇸Twin Falls, Idaho, United States
Saint Anthony's Health
🇺🇸Alton, Illinois, United States
Illinois CancerCare-Bloomington
🇺🇸Bloomington, Illinois, United States
Loyola Center for Health at Burr Ridge
🇺🇸Burr Ridge, Illinois, United States
Illinois CancerCare-Canton
🇺🇸Canton, Illinois, United States
Memorial Hospital of Carbondale
🇺🇸Carbondale, Illinois, United States
SIH Cancer Institute
🇺🇸Carterville, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸Carthage, Illinois, United States
Centralia Oncology Clinic
🇺🇸Centralia, Illinois, United States
Saint Mary's Hospital
🇺🇸Centralia, Illinois, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
John H Stroger Jr Hospital of Cook County
🇺🇸Chicago, Illinois, United States
Cancer Care Specialists of Illinois - Decatur
🇺🇸Decatur, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Illinois CancerCare-Dixon
🇺🇸Dixon, Illinois, United States
Crossroads Cancer Center
🇺🇸Effingham, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare-Galesburg
🇺🇸Galesburg, Illinois, United States
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
🇺🇸Melrose Park, Illinois, United States
Mercy Hospital Saint Louis
🇺🇸Saint Louis, Missouri, United States
Sainte Genevieve County Memorial Hospital
🇺🇸Sainte Genevieve, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
BJC Outpatient Center at Sunset Hills
🇺🇸Sunset Hills, Missouri, United States
Mercy Hospital Washington
🇺🇸Washington, Missouri, United States
Saint Patrick Hospital - Community Hospital
🇺🇸Missoula, Montana, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Missouri Baptist Sullivan Hospital
🇺🇸Sullivan, Missouri, United States
Monmouth Medical Center
🇺🇸Long Branch, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Mercy Hospital Oklahoma City
🇺🇸Oklahoma City, Oklahoma, United States
Saint Charles Health System
🇺🇸Bend, Oregon, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Providence Cancer Institute Clackamas Clinic
🇺🇸Clackamas, Oregon, United States
Bay Area Hospital
🇺🇸Coos Bay, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Saint Charles Health System-Redmond
🇺🇸Redmond, Oregon, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pennsylvania/Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
Providence Regional Cancer System-Aberdeen
🇺🇸Aberdeen, Washington, United States
PeaceHealth Saint Joseph Medical Center
🇺🇸Bellingham, Washington, United States
Providence Regional Cancer System-Centralia
🇺🇸Centralia, Washington, United States
Swedish Cancer Institute-Edmonds
🇺🇸Edmonds, Washington, United States
Providence Regional Cancer Partnership
🇺🇸Everett, Washington, United States
Swedish Cancer Institute-Issaquah
🇺🇸Issaquah, Washington, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Providence Regional Cancer System-Lacey
🇺🇸Lacey, Washington, United States
PeaceHealth Saint John Medical Center
🇺🇸Longview, Washington, United States
Pacific Gynecology Specialists
🇺🇸Seattle, Washington, United States
Swedish Medical Center-Ballard Campus
🇺🇸Seattle, Washington, United States
Swedish Medical Center-Cherry Hill
🇺🇸Seattle, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
PeaceHealth United General Medical Center
🇺🇸Sedro-Woolley, Washington, United States
Providence Regional Cancer System-Shelton
🇺🇸Shelton, Washington, United States
PeaceHealth Southwest Medical Center
🇺🇸Vancouver, Washington, United States
Providence Saint Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
Providence Regional Cancer System-Yelm
🇺🇸Yelm, Washington, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Marshfield Clinic-Minocqua Center
🇺🇸Minocqua, Wisconsin, United States
Cancer Center of Western Wisconsin
🇺🇸New Richmond, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
Cancer Center-Metro Medical Center Bayamon
🇵🇷Bayamon, Puerto Rico
Puerto Rico Hematology Oncology Group
🇵🇷Bayamon, Puerto Rico
Doctors Cancer Center
🇵🇷Manati, Puerto Rico
San Juan Community Oncology Group
🇵🇷San Juan, Puerto Rico
Centro Comprensivo de Cancer de UPR
🇵🇷San Juan, Puerto Rico
PROncology
🇵🇷San Juan, Puerto Rico
San Juan City Hospital
🇵🇷San Juan, Puerto Rico
University of Florida Health Science Center - Jacksonville
🇺🇸Jacksonville, Florida, United States
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Mayo Clinic Hospital in Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States
Mercy Hospital Fort Smith
🇺🇸Fort Smith, Arkansas, United States
CARTI Cancer Center
🇺🇸Little Rock, Arkansas, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
Smilow Cancer Hospital Care Center at Saint Francis
🇺🇸Hartford, Connecticut, United States
Smilow Cancer Center/Yale-New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Saint Luke's Cancer Institute - Boise
🇺🇸Boise, Idaho, United States
Saint Luke's Cancer Institute - Fruitland
🇺🇸Fruitland, Idaho, United States
Western Illinois Cancer Treatment Center
🇺🇸Galesburg, Illinois, United States
Loyola Medicine Homer Glen
🇺🇸Homer Glen, Illinois, United States
Illinois CancerCare-Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Illinois CancerCare-Macomb
🇺🇸Macomb, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
Cancer Care Center of O'Fallon
🇺🇸O'Fallon, Illinois, United States
HSHS Saint Elizabeth's Hospital
🇺🇸O'Fallon, Illinois, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare-Pekin
🇺🇸Pekin, Illinois, United States
OSF Saint Francis Radiation Oncology at Pekin
🇺🇸Pekin, Illinois, United States
Illinois CancerCare-Peoria
🇺🇸Peoria, Illinois, United States
OSF Saint Francis Radiation Oncology at Peoria Cancer Center
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Fairview Clinics and Surgery Center Maple Grove
🇺🇸Maple Grove, Minnesota, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸Maplewood, Minnesota, United States
Saint John's Hospital - Healtheast
🇺🇸Maplewood, Minnesota, United States
Abbott-Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Health Partners Inc
🇺🇸Minneapolis, Minnesota, United States
Monticello Cancer Center
🇺🇸Monticello, Minnesota, United States
New Ulm Medical Center
🇺🇸New Ulm, Minnesota, United States
Fairview Northland Medical Center
🇺🇸Princeton, Minnesota, United States
North Memorial Medical Health Center
🇺🇸Robbinsdale, Minnesota, United States
Mayo Clinic in Rochester
🇺🇸Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸Saint Louis Park, Minnesota, United States
Regions Hospital
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Saint Francis Regional Medical Center
🇺🇸Shakopee, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Minnesota Oncology Hematology PA-Woodbury
🇺🇸Woodbury, Minnesota, United States
Fairview Lakes Medical Center
🇺🇸Wyoming, Minnesota, United States
Saint Louis Cancer and Breast Institute-Ballwin
🇺🇸Ballwin, Missouri, United States
Central Care Cancer Center - Bolivar
🇺🇸Bolivar, Missouri, United States
Cox Cancer Center Branson
🇺🇸Branson, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
Southeast Cancer Center
🇺🇸Cape Girardeau, Missouri, United States
Parkland Health Center - Farmington
🇺🇸Farmington, Missouri, United States
MU Health Care Goldschmidt Cancer Center
🇺🇸Jefferson City, Missouri, United States
Freeman Health System
🇺🇸Joplin, Missouri, United States
Mercy Hospital Joplin
🇺🇸Joplin, Missouri, United States
Lake Regional Hospital
🇺🇸Osage Beach, Missouri, United States
Delbert Day Cancer Institute at PCRMC
🇺🇸Rolla, Missouri, United States
Mercy Clinic-Rolla-Cancer and Hematology
🇺🇸Rolla, Missouri, United States
Heartland Regional Medical Center
🇺🇸Saint Joseph, Missouri, United States
Saint Louis Cancer and Breast Institute-South City
🇺🇸Saint Louis, Missouri, United States
Mercy Hospital South
🇺🇸Saint Louis, Missouri, United States
Missouri Baptist Medical Center
🇺🇸Saint Louis, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Community Medical Center
🇺🇸Toms River, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States