A Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine Versus Standard of Care After Allogeneic Stem Cell Transplantation (SCT) in Participants With Acute Myeloid Leukemia (AML)

Phase 3TerminatedNCT04161885

AbbVie465 enrolled

Overview

The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Overall Survival (OS) in Acute Myeloid Leukemia (AML) participants compared to Best Supportive Care (BSC) when given as maintenance therapy following allogeneic stem cell transplantation (SCT). This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who are greater than or equal to 18 years old; Part 2 (Randomization) which may include participants who are greater than or equal to 12 years old. During Part 1, recommended Phase 3 dose of venetoclax in combination with azacitidine will be determined and during Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with BSC (Part 2 Arm B).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

465

Conditions

Acute Myeloid Leukemia (AML)Cancer

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants must be at least 18 years old for Part 1 and, at least 12 years old for Part 2. * Participant must be diagnosed with Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell transplantation or have received allogeneic stem cell transplantation within the past 60 days. * Blast percentage in bone marrow before transplant must be \< 10%. * Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must be \< 5% after transplant. * Participant meet adequate renal, hepatic and hematologic criteria as described in the protocol. * Participants \>= 17 years old must have a Karnofsky Performance Scale (KPS) score \> 50 and participants between 12 to 16 years old must have a Lansky Play Performance Scale score \> 40. Exclusion Criteria: * History of disease progression during prior treatment with venetoclax. * History of any other malignancy within 2 years prior to study entry, except for: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; Myelodysplastic Syndrome, Myeloproliferative neoplasm (only allowed if it transformed to AML and AML should be the indication for marrow transplantation). * Participant has known infection with HIV or history of being positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. * Presence of clinical or laboratory symptoms/signs of extramedullary myeloid malignancy.

Locations (165)

Arizona Oncology - Scottsdale - Cancer Transplant Institute /ID# 239711

Scottsdale, Arizona, United States

University of Arizona Cancer Center - Tucson /ID# 242507

Tucson, Arizona, United States

University of Arkansas for Medical Sciences /ID# 239804

Little Rock, Arkansas, United States

City of Hope /ID# 213681

Duarte, California, United States

UCHSC Anschultz Cancer Pavilion /ID# 215618

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)

DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax and AZA as described in the protocol and evaluated by the Investigator and the sponsor.

Time frame: Up to the first treatment cycle (28 days)

Overall Survival (OS) (Part 2)

OS is defined as the number of days from the date of randomization to the date of death from any cause.

Time frame: Up to 45 months after the first participant is randomized

Secondary Outcomes

Morphologic Relapse-Free Survival (RFS) (Part 2)

Morphologic relapse from AML defined as bone marrow blasts of \>= 5% or reappearance of blasts in the peripheral blood not attributable to any other cause (e.g., bone marrow regeneration) in at least 2 peripheral blood samples at least one week apart or development of extramedullary disease after achieving a complete remission (CR) or complete remission with incomplete count recovery (CRi); or the date of death from any cause, whichever comes first as determined by Independent Review Committee (IRC).