A Study of Oral Venetoclax Tablets and Oral Azacitidine Versus Oral Azacitidine as Maintenance Therapy in Adult Participants With Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy

Study Overview
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Brief Summary
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This study will be conducted in two parts. Part 1 will be the Dose Confirmation portion to determine recommended Phase 3 dose (RPTD) of venetoclax in combination with AZA. Part 3 will be the Dose Finding portion to determine RPTD of venetoclax in combination with CC-486. Part 2 and Part 3 Randomization of the study were removed.

Official Title
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A Multicenter, Phase 3 Study of Venetoclax and Oral Azacitidine Versus Oral Azacitidine as Maintenance Therapy for Patients With Acute Myeloid Leukemia in First Remission After Conventional Chemotherapy (VIALE-M)

Conditions
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Acute Myeloid Leukemia (AML)

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Azacitidine
* Drug: CC-486


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of newly diagnosed acute myeloid leukemia (AML). Participant meets the following disease activity criteria: Confirmation of AML by World Health Organization (WHO) criteria (2016) and have confirmed complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following completion of intensive induction and consolidation chemotherapies. Achieved first CR + CRi within 120 days of first dose of study drug or be no more than 75 days since last dose of intensive conventional (including both induction and consolidation) chemotherapies. AML has intermediate or poor risk cytogenetics per National Comprehensive Cancer Network (NCCN) 2016 criteria. Eastern Cooperative Oncology Group (ECOG) performance status <= 2. Participant must have adequate hematologic, renal, and liver function laboratory values as described in the protocol. Exclusion Criteria: History of acute promyelocytic leukemia (APL). History of active central nervous system involvement with acute myeloid leukemia (AML).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Confirmation<br>Participants will receive venetoclax once daily (QD) (Days 1-28) for up to 48 cycles, azacitidine (AZA) QD on Days 1-5 of each 28 day cycle for up to 6 cycles. | Drug: Venetoclax<br>* Tablet: Oral<br>* Other names: Venclexta;Drug: Azacitidine<br>* Subcutaneous (SC) or intravenous (IV) injection<br>|
| Experimental: Part 3 (Dose Finding): Dose Escalation<br>Participants will receive venetoclax QD for up to 24 cycles, CC-486 QD on Days 1 to 14 of each 28-day cycle for up to 24 cycles to determine recommended phase 3 dose (RPTD). | Drug: Venetoclax<br>* Tablet: Oral<br>* Other names: Venclexta;Drug: CC-486<br>* Tablet; Oral<br>* Other names: Azacitidine;|
| Experimental: Part 3 (Dose Finding): Safety Expansion<br>Participants will receive venetoclax QD for up to 24 cycles, CC-486 QD on Days 1 to 14 of each 28-day cycle for up to 24 cycles at the RPTD. | Drug: Venetoclax<br>* Tablet: Oral<br>* Other names: Venclexta;Drug: CC-486<br>* Tablet; Oral<br>* Other names: Azacitidine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-Limiting Toxicities (DLTs) (Part 1) | DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax as described in the protocol and evaluated by the Investigator and the sponsor. | Time from treatment of first participant to 20th participant reaching end of cycle 1, approximately 7 Months | 
| Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination with Azacitidine (CC-486) (Part 3 Dose Finding Portion) | DLTs are hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax in combination with CC-486 as described in the protocol and evaluated by the Investigator and the sponsor. | Time from treatment of first participant to the 14th patient in Safety Expansion reaching the end of Cycle 1, approximately 16 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CC-486, Acute myeloid leukemia (AML), Venetoclax, Azacitidine, Maintenance Therapy, Conventional Chemotherapy, Best supportive care (BSC)