Ignite Creation Date:
2025-12-24 @ 6:56 PM
Ignite Modification Date:
2026-01-04 @ 2:58 AM
Study NCT ID:
NCT03862157
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-07-30
First Post:
2019-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
A Phase I/II Study of Azacitidine, Venetoclax and Pevonedistat in Adults With Newly Diagnosed Secondary or Therapy-Related AML
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial studies the best dose of venetoclax when given together with azacitidine and pevonedistat and to see how well it works in treating patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, 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. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Pevonedistat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine, venetoclax, and pevonedistat may work better in treating patients with acute myeloid leukemia.
Detailed Description:
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) of venetoclax in combination with azacitidine and pevonedistat in patients with previously untreated secondary acute myeloid leukemia (AML). (Phase I) II. To determine the efficacy of the combination regimen, as defined by the rate of complete response (CR) plus complete response with incomplete bone marrow recovery (CRi) within 6 cycles of treatment. (Phase II \[AML\]) III. To determine the efficacy of the combination regimen, as defined by the rate of CR within 6 cycles of treatment. (Phase II \[myelodysplastic syndrome (MDS) Newly Diagnosed\]) IV. To determine the overall response rate (defined as CR + marrow CR \[mCR\] + partial remission \[PR\] + hematological improvement \[HI\]) within 6 cycles of treatment. (Phase II \[MDS/chronic myelomonocytic leukemia (CMML) post-hypomethylating agent (HMA) failure\])
SECONDARY OBJECTIVES:
I. To determine efficacy outcomes, including CR rate, leukemia response rate (CR + CRi + partial response \[PR\] + morphologic leukemia free state \[MLFS\]), minimal residual disease (MRD) negativity by flow cytometry, duration of response, transformation to AML (in the MDS cohorts), relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS).
II. To determine the safety of the combination regimen.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7, and pevonedistat IV over 60 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, and then every 6 months thereafter.
I. To determine the maximum-tolerated dose (MTD) of venetoclax in combination with azacitidine and pevonedistat in patients with previously untreated secondary acute myeloid leukemia (AML). (Phase I) II. To determine the efficacy of the combination regimen, as defined by the rate of complete response (CR) plus complete response with incomplete bone marrow recovery (CRi) within 6 cycles of treatment. (Phase II \[AML\]) III. To determine the efficacy of the combination regimen, as defined by the rate of CR within 6 cycles of treatment. (Phase II \[myelodysplastic syndrome (MDS) Newly Diagnosed\]) IV. To determine the overall response rate (defined as CR + marrow CR \[mCR\] + partial remission \[PR\] + hematological improvement \[HI\]) within 6 cycles of treatment. (Phase II \[MDS/chronic myelomonocytic leukemia (CMML) post-hypomethylating agent (HMA) failure\])
SECONDARY OBJECTIVES:
I. To determine efficacy outcomes, including CR rate, leukemia response rate (CR + CRi + partial response \[PR\] + morphologic leukemia free state \[MLFS\]), minimal residual disease (MRD) negativity by flow cytometry, duration of response, transformation to AML (in the MDS cohorts), relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS).
II. To determine the safety of the combination regimen.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
Patients receive venetoclax orally (PO) once daily (QD) on days 1-28, azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7, and pevonedistat IV over 60 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days, and then every 6 months thereafter.
Study Oversight
Has Oversight DMC:
False
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?: