Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03862157|
Recruitment Status : Recruiting
First Posted : March 5, 2019
Last Update Posted : March 11, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Eosinophilic Leukemia, Not Otherwise Specified Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Essential Thrombocythemia Myelodysplastic Syndrome Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myeloid Neoplasm Myeloproliferative Neoplasm Myeloproliferative Neoplasm, Unclassifiable Overt Primary Myelofibrosis Polycythemia Vera Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase Prefibrotic/Early Primary Myelofibrosis||Drug: Azacitidine Drug: Pevonedistat Drug: Venetoclax||Phase 1 Phase 2|
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])
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Azacitidine, Venetoclax and Pevonedistat in Adults With Newly Diagnosed Secondary or Therapy-Related AML|
|Actual Study Start Date :||February 27, 2019|
|Estimated Primary Completion Date :||January 1, 2024|
|Estimated Study Completion Date :||January 1, 2024|
Experimental: Treatment (venetoclax, azacitidine, pevonedistat)
Patients receive venetoclax PO QD on days 1-28, azacitidine IV or 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.
Given IV or SC
- Incidence of dose-limiting toxicities (DLTs) (Phase I) [ Time Frame: Up to 28 days from treatment start date ]
- Complete response (CR)/complete response with incomplete bone marrow recovery (CRi) rate (Phase II acute myeloid leukemia cohort) [ Time Frame: Up to 168 days (6 cycles) ]
- Complete response rate of the combination regimen (Phase II newly diagnosed myelodysplastic syndrome [MDS]/chronic myelomonocytic leukemia [CMML] cohort) [ Time Frame: Up to 168 days (6 cycles) ]
- CR + marrow CR (mCR) + partial remission (PR) + hematological improvement (HI) rate of the combination regimen (Phase II MDS/CMML post-hypomethylating agent failure cohort) [ Time Frame: Up to 168 days (6 cycles) ]
- Leukemia response rate (CR + CRi + partial response [PR] + morphologic leukemia-free state [MLFS]) [ Time Frame: Up to 5 years ]
- Minimal residual disease negativity rate [ Time Frame: Up to cycle 24, day 28 ]Measured by flow cytometry.
- Duration of response [ Time Frame: Time from response to relapse, assessed up to 5 years ]
- Relapse-free survival (RFS) [ Time Frame: Time from response to relapse, death, or last follow-up, assessed up to 5 years ]
- Event-free survival (EFS) [ Time Frame: Time from initiation of treatment to relapse, death or last follow-up, assessed up to 5 years ]
- Overall survival (OS) [ Time Frame: Time from initiation of treatment to death or last follow-up, assessed up to 5 years ]
- Incidence of adverse events [ Time Frame: Up to 30 days after last dose of study drugs ]Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03862157
|Contact: Nicholas Shortemail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Nicholas Short 713-792-8760|
|Principal Investigator: Nicholas Short|
|Principal Investigator:||Nicholas Short||M.D. Anderson Cancer Center|