Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03808610 |
Recruitment Status :
Recruiting
First Posted : January 17, 2019
Last Update Posted : April 18, 2024
|
Tracking Information | |||||
---|---|---|---|---|---|
First Submitted Date ICMJE | January 16, 2019 | ||||
First Posted Date ICMJE | January 17, 2019 | ||||
Last Update Posted Date | April 18, 2024 | ||||
Actual Study Start Date ICMJE | April 3, 2019 | ||||
Estimated Primary Completion Date | December 31, 2026 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
|
||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
|
||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
Apoptotic protein expression and Bcl-2 dependency [ Time Frame: Up to 4 years ] Apoptotic protein expression and Bcl-2 dependency will be correlated on response and resistance to the combination regimen.
|
||||
Original Other Pre-specified Outcome Measures | Same as current | ||||
Descriptive Information | |||||
Brief Title ICMJE | Low-Intensity Chemotherapy and Venetoclax in Treating Patients With Relapsed or Refractory B- or T-Cell Acute Lymphoblastic Leukemia | ||||
Official Title ICMJE | Phase I/II Study of the Combination of Low-Intensity Chemotherapy and Venetoclax (ABT-199) in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) | ||||
Brief Summary | This phase I/II trial studies the side effects and best dose of venetoclax and how well it works in combination with low-intensity chemotherapy in patients with B- or T-cell acute lymphoblastic leukemia that has not responded to treatment or that has come back. Venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, including vincristine, cyclophosphamide, dexamethasone, rituximab, methotrexate, and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax with low-intensity chemotherapy may work better in treating patient with B- or T-cell acute lymphoblastic leukemia. | ||||
Detailed Description | PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose-limited toxicities (DLTs) of venetoclax in combination with low-intensity chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) (Phase I). II. Evaluate the overall response rate (complete response [CR] + CR with inadequate count recovery [CRi]) of the regimen after 2 cycles. (Phase II) SECONDARY OBJECTIVES: I. Evaluate other clinical efficacy endpoints (minimal residual disease [MRD] negativity, duration of response [DOR], event-free survival [EFS] and overall survival [OS]). II. Determine the safety of the combination regimen. EXPLORATORY OBJECTIVES: I. To correlate apoptotic protein expression and Bcl-2 dependency on response and resistance to the combination regimen. OUTLINE: This is a phase I, dose-escalation study of venetoclax, followed by a phase II study. CHEMOTHERAPY AND VENETOCLAX: CYCLE 1: Patients receive venetoclax orally (PO) once daily (QD) on days 1-21, vincristine intravenously (IV) over 15 minutes on days 7 and 17, cyclophosphamide IV twice daily (BID) over 3 hours on days 7-9, and dexamethasone IV over 30 minutes or PO QD on days 7-10 and 17-20. Patients may also receive rituximab IV over 4-6 hours on days 7 and 17 per physician discretion. CYCLES 2, 4, 6, and 8: Patients receive venetoclax PO QD on days 1-21, methotrexate IV over 24 hours on day 1, and cytarabine IV BID over 3 hours on days 2 and 3. Patients may also receive rituximab IV over 4-6 hours on days 1 and 8 per physician discretion. CYCLES 3, 5, and 7: Patients receive venetoclax PO QD on days 1-21, cyclophosphamide IV BID over 3 hours on days 1-3, vincristine IV over 15 minutes on days 1 and 11, and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients may also receive rituximab IV over 4-6 hours on days 1 and 11 per physician discretion. T-CELL ALL: After the first 4 cycles, patients receive nelarabine IV over 2 hours on days 1-5 and pegaspargase IV over 2 hours on day 5. Cycles repeat every 28 days for 2 cycles (after cycle 4 and 5) in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients may receive prednisone PO QD on days 1-5, vincristine IV over 15 minutes on day 1, and venetoclax, PO QD on days 1-21. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. T-CELL ALL (MAINTENANCE THERAPY): After the first 5 cycles of maintenance therapy, patients who received nelarabine and pegaspargase will receive nelarabine IV QD over 2 hours on days 1-5 and pegaspargase IV over 2 hours on day 5 during maintenance cycles 6 and 7 instead of prednisone, vincristine, and venetoclax. After completion of study treatment, patients are followed up for 30 days and then every 3 months thereafter. |
||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||
Condition ICMJE |
|
||||
Intervention ICMJE |
|
||||
Study Arms ICMJE | Experimental: Experimental (venetoclax, vincristine, cyclophosphamide)
See Detailed Description.
Interventions:
|
||||
Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||
Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
50 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | December 31, 2026 | ||||
Estimated Primary Completion Date | December 31, 2026 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||
Sex/Gender ICMJE |
|
||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
|
||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT03808610 | ||||
Other Study ID Numbers ICMJE | 2016-0629 NCI-2018-03360 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2016-0629 ( Other Identifier: M D Anderson Cancer Center ) |
||||
Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
|
||||
IPD Sharing Statement ICMJE | Not Provided | ||||
Current Responsible Party | M.D. Anderson Cancer Center | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor ICMJE | M.D. Anderson Cancer Center | ||||
Original Study Sponsor ICMJE | Same as current | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
|
||||
PRS Account | M.D. Anderson Cancer Center | ||||
Verification Date | April 2024 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |