A Phase IB/II Study of Venetoclax (ABT-199) in Combination With Liposomal Vincristine or Vincristine Sulfate in Patients With Relapsed or Refractory T-Cell or B-Cell Acute Lymphoblastic Leukemia
| Registry | NCT03504644 |
|---|---|
| Status | Active not recruiting |
| Phase | Phase 1 / Phase 2 |
| Study type | Interventional; non randomized, parallel, masking: none, treatment |
| Enrollment | 40 (Actual) |
| Sponsor | ECOG-ACRIN Cancer Research Group (Network); collaborators: National Cancer Institute (NCI) |
| Conditions | Recurrent Adult Lymphoblastic Lymphoma, Recurrent B Acute Lymphoblastic Leukemia, Recurrent B Lymphoblastic Lymphoma, Recurrent T Acute Lymphoblastic Leukemia, Recurrent T Lymphoblastic Lymphoma, Refractory B Acute Lymphoblastic Leukemia, Refractory B Lymphoblastic Lymphoma, Refractory T Acute Lymphoblastic Leukemia, Refractory T Lymphoblastic Lymphoma |
| Interventions | Biospecimen Collection, Computed Tomography, Lumbar Puncture, Positron Emission Tomography, Venetoclax, Vincristine Liposomal, Vincristine Sulfate (Procedure, drug) |
| Dates | start 2018-08-13, primary completion 2025-07-22, completion 2028-12-31 (estimated), first posted 2018-04-20, last updated 2026-10-06 |
| Locations | 170 sites in United States, Puerto Rico |
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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.
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Phase Ib (venetoclax, vincristine liposomal) | Experimental | Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Lumbar Puncture; Procedure: Positron Emission Tomography; Drug: Venetoclax; Drug: 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) | Experimental | Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Lumbar Puncture; Procedure: Positron Emission Tomography; Drug: Venetoclax; Drug: Vincristine Liposomal; Drug: 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. |
Sex: All, ages: 18 Years to any
Inclusion Criteria: * 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 Exclusion Criteria: * 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
| Milestone | Phase Ib Arm A (Dose Level 1) | Phase Ib Arm B (Dose Level 2) | Phase Ib Arm C (Dose Level 3) | Phase II (Venetoclax, Vincristine Liposomal/Sulfate) - Phenotype B-cell ALL/LL | Phase II (Venetoclax, Vincristine Liposomal/Sulfate) - Phenotype T-cell ALL/LL |
|---|---|---|---|---|---|
| Started | 3 | 12 | 3 | 13 | 9 |
| Never started assigned therapy | 0 | 0 | 0 | 1 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 3 | 12 | 3 | 13 | 9 |
Time frame: Assessed every treatment cycle while on treatment and for 30 days after the end of treatment, up to 7 years
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Phase Ib Arm A (Dose Level 1) | 0/3 (0.0%) | 2/3 (66.7%) | 3/3 (100.0%) |
| Phase Ib Arm B (Dose Level 2) | 2/12 (16.7%) | 9/12 (75.0%) | 12/12 (100.0%) |
| Phase Ib Arm C (Dose Level 3) | 0/3 (0.0%) | 3/3 (100.0%) | 3/3 (100.0%) |
| Phase II (Venetoclax, Vincristine Liposomal/Sulfate) | 17/22 (77.3%) | 12/21 (57.1%) | 21/21 (100.0%) |
| Term | Organ system | Phase Ib Arm A (Dose Level 1) | Phase Ib Arm B (Dose Level 2) | Phase Ib Arm C (Dose Level 3) | Phase II (Venetoclax, Vincristine Liposomal/Sulfate) |
|---|---|---|---|---|---|
| Ear and labyrinth disorders - Other, specify | Ear and labyrinth disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Anemia | Blood and lymphatic system disorders | 0/3 | 0/12 | 1/3 | 1/21 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0/3 | 2/12 | 3/3 | 4/21 |
| Myocardial infarction | Cardiac disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Sinus tachycardia | Cardiac disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Cardiac disorders - Other, specify | Cardiac disorders | 1/3 | 0/12 | 0/3 | 0/21 |
| Death NOS | General disorders and administration site conditions | 0/3 | 0/12 | 0/3 | 1/21 |
| Edema face | General disorders and administration site conditions | 0/3 | 0/12 | 0/3 | 1/21 |
| Fever | General disorders and administration site conditions | 1/3 | 1/12 | 1/3 | 0/21 |
| Non-cardiac chest pain | General disorders and administration site conditions | 0/3 | 0/12 | 1/3 | 0/21 |
| Disease progression | General disorders and administration site conditions | 0/3 | 2/12 | 0/3 | 2/21 |
| Pruritus | Skin and subcutaneous tissue disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Abdominal pain | Gastrointestinal disorders | 0/3 | 2/12 | 0/3 | 0/21 |
| Constipation | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Diarrhea | Gastrointestinal disorders | 0/3 | 1/12 | 1/3 | 0/21 |
| Dysphagia | Gastrointestinal disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Gastric hemorrhage | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Ileus | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Mucositis oral | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 1/21 |
| Nausea | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 1/21 |
| Vomiting | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Appendicitis | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Enterocolitis infectious | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Lung infection | Infections and infestations | 0/3 | 2/12 | 0/3 | 2/21 |
| Sepsis | Infections and infestations | 0/3 | 2/12 | 1/3 | 2/21 |
| Skin infection | Infections and infestations | 0/3 | 1/12 | 0/3 | 1/21 |
| Bacteremia | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Herpes simplex reactivation | Infections and infestations | 0/3 | 0/12 | 0/3 | 1/21 |
| Fungemia | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Infections and infestations - Other, specify | Infections and infestations | 0/3 | 0/12 | 0/3 | 1/21 |
| Fall | Injury, poisoning and procedural complications | 0/3 | 0/12 | 0/3 | 2/21 |
| Alkaline phosphatase increased | Investigations | 0/3 | 0/12 | 1/3 | 0/21 |
| Blood bilirubin increased | Investigations | 0/3 | 0/12 | 0/3 | 1/21 |
| Neutrophil count decreased | Investigations | 0/3 | 2/12 | 1/3 | 1/21 |
| Platelet count decreased | Investigations | 0/3 | 1/12 | 1/3 | 2/21 |
| White blood cell decreased | Investigations | 0/3 | 0/12 | 2/3 | 1/21 |
| Anorexia | Metabolism and nutrition disorders | 0/3 | 0/12 | 1/3 | 1/21 |
| Hypercalcemia | Metabolism and nutrition disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Hypokalemia | Metabolism and nutrition disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Hypomagnesemia | Metabolism and nutrition disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Hyponatremia | Metabolism and nutrition disorders | 1/3 | 0/12 | 0/3 | 0/21 |
| Back pain | Musculoskeletal and connective tissue disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Seizure | Nervous system disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Stroke | Nervous system disorders | 1/3 | 0/12 | 0/3 | 0/21 |
| Nervous system disorders - Other, specify | Nervous system disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 0/3 | 0/12 | 0/3 | 1/21 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 0/3 | 1/12 | 0/3 | 2/21 |
| Hypotension | Vascular disorders | 0/3 | 1/12 | 1/3 | 1/21 |
| Term | Organ system | Phase Ib Arm A (Dose Level 1) | Phase Ib Arm B (Dose Level 2) | Phase Ib Arm C (Dose Level 3) | Phase II (Venetoclax, Vincristine Liposomal/Sulfate) |
|---|---|---|---|---|---|
| Ear and labyrinth disorders - Other, specify | Ear and labyrinth disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Anemia | Blood and lymphatic system disorders | 3/3 | 8/12 | 3/3 | 14/21 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0/3 | 4/12 | 2/3 | 0/21 |
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Atrial fibrillation | Cardiac disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Conduction disorder | Cardiac disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Heart failure | Cardiac disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Palpitations | Cardiac disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Pericardial effusion | Cardiac disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Sinus tachycardia | Cardiac disorders | 0/3 | 1/12 | 1/3 | 1/21 |
| Cardiac disorders - Other, specify | Cardiac disorders | 0/3 | 2/12 | 0/3 | 0/21 |
| Chills | General disorders and administration site conditions | 1/3 | 3/12 | 1/3 | 1/21 |
| Edema limbs | General disorders and administration site conditions | 2/3 | 3/12 | 1/3 | 4/21 |
| Fatigue | General disorders and administration site conditions | 1/3 | 7/12 | 3/3 | 8/21 |
| Fever | General disorders and administration site conditions | 0/3 | 5/12 | 1/3 | 5/21 |
| Non-cardiac chest pain | General disorders and administration site conditions | 0/3 | 1/12 | 1/3 | 2/21 |
| Pain | General disorders and administration site conditions | 0/3 | 3/12 | 2/3 | 2/21 |
| Generalized edema | General disorders and administration site conditions | 0/3 | 1/12 | 0/3 | 0/21 |
| General disorders and administration site conditions - Other, specify | General disorders and administration site conditions | 0/3 | 1/12 | 1/3 | 1/21 |
| Alopecia | Skin and subcutaneous tissue disorders | 1/3 | 3/12 | 0/3 | 0/21 |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | 0/3 | 1/12 | 0/3 | 1/21 |
| Pain of skin | Skin and subcutaneous tissue disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Pruritus | Skin and subcutaneous tissue disorders | 1/3 | 0/12 | 0/3 | 2/21 |
| Purpura | Skin and subcutaneous tissue disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 1/3 | 0/12 | 0/3 | 0/21 |
| Skin ulceration | Skin and subcutaneous tissue disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | 1/3 | 4/12 | 0/3 | 3/21 |
| Adrenal insufficiency | Endocrine disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Abdominal pain | Gastrointestinal disorders | 0/3 | 4/12 | 2/3 | 5/21 |
| Anal hemorrhage | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Bloating | Gastrointestinal disorders | 1/3 | 0/12 | 0/3 | 0/21 |
| Colitis | Gastrointestinal disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Constipation | Gastrointestinal disorders | 1/3 | 4/12 | 3/3 | 7/21 |
| Diarrhea | Gastrointestinal disorders | 1/3 | 4/12 | 3/3 | 5/21 |
| Dry mouth | Gastrointestinal disorders | 1/3 | 1/12 | 0/3 | 1/21 |
| Dyspepsia | Gastrointestinal disorders | 1/3 | 0/12 | 1/3 | 0/21 |
| Enterocolitis | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 1/21 |
| Fecal incontinence | Gastrointestinal disorders | 0/3 | 0/12 | 1/3 | 0/21 |
| Gastroesophageal reflux disease | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Mucositis oral | Gastrointestinal disorders | 0/3 | 1/12 | 0/3 | 1/21 |
| Nausea | Gastrointestinal disorders | 3/3 | 8/12 | 3/3 | 11/21 |
| Vomiting | Gastrointestinal disorders | 3/3 | 4/12 | 2/3 | 7/21 |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | 1/3 | 2/12 | 2/3 | 1/21 |
| Immune system disorders - Other, specify | Immune system disorders | 0/3 | 1/12 | 0/3 | 0/21 |
| Kidney infection | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Sepsis | Infections and infestations | 0/3 | 0/12 | 2/3 | 0/21 |
| Sinusitis | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Urinary tract infection | Infections and infestations | 0/3 | 0/12 | 0/3 | 2/21 |
| Bacteremia | Infections and infestations | 0/3 | 2/12 | 1/3 | 0/21 |
| Thrush | Infections and infestations | 0/3 | 1/12 | 0/3 | 0/21 |
| Infections and infestations - Other, specify | Infections and infestations | 1/3 | 1/12 | 0/3 | 1/21 |
| Bruising | Injury, poisoning and procedural complications | 0/3 | 1/12 | 0/3 | 3/21 |
| Fall | Injury, poisoning and procedural complications | 1/3 | 0/12 | 0/3 | 3/21 |
| Activated partial thromboplastin time prolonged | Investigations | 0/3 | 1/12 | 0/3 | 1/21 |
| Alanine aminotransferase increased | Investigations | 1/3 | 6/12 | 3/3 | 4/21 |
| Alkaline phosphatase increased | Investigations | 2/3 | 2/12 | 2/3 | 4/21 |
| Aspartate aminotransferase increased | Investigations | 1/3 | 8/12 | 3/3 | 12/21 |
| Blood bilirubin increased | Investigations | 1/3 | 2/12 | 1/3 | 3/21 |
| Creatinine increased | Investigations | 1/3 | 0/12 | 0/3 | 3/21 |
| Electrocardiogram QT corrected interval prolonged | Investigations | 0/3 | 0/12 | 1/3 | 0/21 |
79 more terms not shown.
| Facility | City | Country | Status |
|---|---|---|---|
| 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 | |
| University of Florida Health Science Center - Jacksonville | Jacksonville, Florida | 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 | |
| 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 | |
| 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 | |
| Marjorie Weinberg Cancer Center at Loyola-Gottlieb | Melrose Park, 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 | |
| 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 | |
| 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 | |
| Rice Memorial Hospital | Willmar, 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 |
70 more sites not listed.
NIH grants: U10CA180820