Ignite Creation Date:
2024-05-06 @ 4:06 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04872790
Status:
RECRUITING
Last Update Posted:
2023-12-20
First Post:
2021-03-19
Brief Title:
Venetoclax Dasatinib Prednisone Rituximab and Blinatumomab for the Treatment of Newly Diagnosed or Relapsed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia
Sponsor:
OHSU Knight Cancer Institute
Organization:
OHSU Knight Cancer Institute
Study Overview
Official Title:
A Dose-Finding Phase Ib Study of the Oral BCL-2 Inhibitor Venetoclax ABT-199 in Combination With Standard Induction Therapy Dasatinib Prednisone and Rituximab in CD20 Patients in Adult Patients With Newly Diagnosed and Relapsed Philadelphia Chromosome Positive ALL Ph ALL and Ph MPAL
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial studies the effects of venetoclax in combination with dasatinib prednisone rituximab and blinatumomab in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia ALL that is newly diagnosed or that has come back relapsed Venetoclax may stop the growth of cancer cells by blocking Bcl-2 a protein needed for cancer cell survival Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Anti-inflammatory drugs such as prednisone lower the bodys immune response and are used with other drugs in the treatment of some types of cancer Rituximab and blinatumomab are monoclonal antibody that may interfere with the ability of cancer cells to grow and spread Giving venetoclax in combination with dasatinib prednisone and rituximab and blinatumomab may help treat patients with newly diagnosed or relapsed Philadelphia chromosome positive acute lymphoblastic leukemia
Detailed Description:
PRIMARY OBJECTIVES
I Determine the maximum tolerated dose MTD andor a recommended phase II dose RP2D of venetoclax in combination with dasatinib
II Evaluate the safety of venetoclax in combination with dasatinib by assessing the frequency type and severity of adverse events
SECONDARY OBJECTIVES
I Assess preliminary response to venetoclax in combination with dasatinib based on minimal residual disease MRD negativity
II Estimate progression-free and overall survival
EXPLORATORY OBJECTIVES
I Evaluate the distribution of BCR-ABL fusion sub-types II Assess changes in BCL-family dependence III Presence of co-occurring leukemia-specific mutations IV Assess ex vivo sensitivity to venetoclax and dasatinib using inhibitor plates and colorimetric cell viability MTS assay
OUTLINE This is dose-escalation study of venetoclax
INDUCTION PHASE CYCLE 1 Patients receive prednisone orally PO once daily QD on days -6 to 21 and rapid taper from days 22-28 dasatinib PO QD days 1-28 venetoclax PO QD days 3-28 or days 3-21 rituximab for CD20 patients intravenously IV on days 8 and 15 and methotrexate intrathecally IT once during week 1 and once during week 3 as prophylaxis or once a week QW as therapy in the absence of disease progression or unacceptable toxicity
INDUCTION PHASE CYCLES 2-3 Patients receive dasatinib PO QD days 1-28 venetoclax PO QD on days 1-28 or 1-21 rituximab for CD20 patients IV on days 1 and 15 and methotrexate IT on days 1 and 15 Treatment repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity Patients with clinical benefit may continue to receive treatment for up to 12 months per the discretion of the physician
CONSOLIDATION CYCLES 4 AND 5 ALL PATIENTS ONLY Patients receive blinatumomab IV on days 1-28 Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity Patients continue to receive dasatinib PO QD and venetoclax PO QD as taken in cycles 1-3 and if clinically indicated methotrexate IT on days 1 and 15 Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo bone marrow biopsy and aspiration lumbar puncture and blood sample collection throughout the study
After completion of study treatment patients are followed up at 4 weeks and then every 12 weeks for up to 1 year
I Determine the maximum tolerated dose MTD andor a recommended phase II dose RP2D of venetoclax in combination with dasatinib
II Evaluate the safety of venetoclax in combination with dasatinib by assessing the frequency type and severity of adverse events
SECONDARY OBJECTIVES
I Assess preliminary response to venetoclax in combination with dasatinib based on minimal residual disease MRD negativity
II Estimate progression-free and overall survival
EXPLORATORY OBJECTIVES
I Evaluate the distribution of BCR-ABL fusion sub-types II Assess changes in BCL-family dependence III Presence of co-occurring leukemia-specific mutations IV Assess ex vivo sensitivity to venetoclax and dasatinib using inhibitor plates and colorimetric cell viability MTS assay
OUTLINE This is dose-escalation study of venetoclax
INDUCTION PHASE CYCLE 1 Patients receive prednisone orally PO once daily QD on days -6 to 21 and rapid taper from days 22-28 dasatinib PO QD days 1-28 venetoclax PO QD days 3-28 or days 3-21 rituximab for CD20 patients intravenously IV on days 8 and 15 and methotrexate intrathecally IT once during week 1 and once during week 3 as prophylaxis or once a week QW as therapy in the absence of disease progression or unacceptable toxicity
INDUCTION PHASE CYCLES 2-3 Patients receive dasatinib PO QD days 1-28 venetoclax PO QD on days 1-28 or 1-21 rituximab for CD20 patients IV on days 1 and 15 and methotrexate IT on days 1 and 15 Treatment repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity Patients with clinical benefit may continue to receive treatment for up to 12 months per the discretion of the physician
CONSOLIDATION CYCLES 4 AND 5 ALL PATIENTS ONLY Patients receive blinatumomab IV on days 1-28 Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity Patients continue to receive dasatinib PO QD and venetoclax PO QD as taken in cycles 1-3 and if clinically indicated methotrexate IT on days 1 and 15 Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity Patients undergo bone marrow biopsy and aspiration lumbar puncture and blood sample collection throughout the study
After completion of study treatment patients are followed up at 4 weeks and then every 12 weeks for up to 1 year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| STUDY00022691 | OTHER | OHSU Knight Cancer Institute | None |
| NCI-2021-01791 | REGISTRY | None | None |