Acute Myeloid Leukemia (AML)
Conditions
Keywords
Acute myeloid leukemia (AML), Venetoclax, Azacitidine (AZA), Maintenance Therapy, Conventional Chemotherapy, Best supportive care (BSC)
Brief summary
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 azacitidine (AZA). Part 3 will be the Dose Finding portion to determine RPTD of venetoclax in combination with AZA. Part 2 and Part 3 Randomization of the study were removed.
Interventions
DRUGVenetoclax
Tablet: Oral
DRUGAzacitidine
Subcutaneous (SC) or intravenous (IV) injection
Sponsors
AbbVie
Roche-Genentech
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Up to 28 days (Cycle 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. |
| Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Up to 28 days (Cycle 1) | DLTs are hematologic toxicities consisting of any Grade ≥ 3 neutropenia or thrombocytopenia lasting more than 7 days and nonhematologic toxicities as described in the protocol and evaluated by the Investigator and the Sponsor. In addition, AEs that lead to omitting \> 20% of the scheduled dose within the cycle is considered as a DLT unless clearly related to underlying disease. Treatment delay due to toxicity lasting greater than 14 days since the last dose of Venetoclax is also considered a DLT. |
Countries
Australia, Canada, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Puerto Rico, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 Participants will receive venetoclax once daily (QD) (Days 1-28) for up to 24 cycles, azacitidine (AZA) QD on Days 1-5 of each 28 day cycle for up to 6 cycles.
Venetoclax: Tablet: Oral
Azacitidine: Subcutaneous (SC) or intravenous (IV) injection | 23 |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 Participants will receive venetoclax once daily (QD) (Days 1-28) for up to 24 cycles, azacitidine (AZA) QD on Days 1-5 of each 28 day cycle for up to 6 cycles.
Venetoclax: Tablet: Oral
Azacitidine: Subcutaneous (SC) or intravenous (IV) injection | 23 |
| Part 1: Venetoclax 400 mg + Azacitidine 50 mg/m^2 Participants will receive venetoclax once daily (QD) (Days 1-28) for up to 24 cycles, azacitidine (AZA) QD on Days 1-5 of each 28 day cycle for up to 6 cycles.
Venetoclax: Tablet: Oral
Azacitidine: Subcutaneous (SC) or intravenous (IV) injection | 20 |
| Part 3: Dose Level 1 - Venetoclax 400mg + CC-486 200mg Participants will receive venetoclax QD for up to 24 cycles, AZA QD on Days 1 to 14 of each 28-day cycle for up to 24 cycles to determine recommended phase 3 dose (RPTD).
Venetoclax: Tablet: Oral
Azacitidine: Oral Tablet | 30 |
| Part 3: Dose Level 2 - Venetoclax 400mg + CC-486 300mg Participants will receive venetoclax QD for up to 24 cycles, AZA QD on Days 1 to 14 of each 28-day cycle for up to 24 cycles at the RPTD.
Venetoclax: Tablet: Oral
Azacitidine: Oral Tablet | 16 |
| Total | 112 |
Baseline characteristics
| Characteristic | Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Total | Part 3: Dose Level 2 - Venetoclax 400mg + CC-486 300mg | Part 3: Dose Level 1 - Venetoclax 400mg + CC-486 200mg | Part 1: Venetoclax 400 mg + Azacitidine 50 mg/m^2 | Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 |
|---|---|---|---|---|---|---|
| Age, Continuous | 53.1 years STANDARD_DEVIATION 13.97 | 55.78 years STANDARD_DEVIATION 14.75 | 54.1 years STANDARD_DEVIATION 16.94 | 58.8 years STANDARD_DEVIATION 12.7 | 55.6 years STANDARD_DEVIATION 16.26 | 57.3 years STANDARD_DEVIATION 13.89 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 27 Participants | 2 Participants | 5 Participants | 8 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 84 Participants | 14 Participants | 25 Participants | 12 Participants | 16 Participants |
| Sex: Female, Male Female | 13 Participants | 56 Participants | 6 Participants | 16 Participants | 10 Participants | 11 Participants |
| Sex: Female, Male Male | 10 Participants | 56 Participants | 10 Participants | 14 Participants | 10 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 23 | 5 / 23 | 1 / 20 | 1 / 30 | 1 / 16 |
| other Total, other adverse events | 21 / 23 | 22 / 23 | 20 / 20 | 29 / 30 | 16 / 16 |
| serious Total, serious adverse events | 5 / 23 | 7 / 23 | 5 / 20 | 5 / 30 | 3 / 16 |
Outcome results
Primary
Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion)
DLTs are hematologic toxicities consisting of any Grade ≥ 3 neutropenia or thrombocytopenia lasting more than 7 days and nonhematologic toxicities as described in the protocol and evaluated by the Investigator and the Sponsor. In addition, AEs that lead to omitting \> 20% of the scheduled dose within the cycle is considered as a DLT unless clearly related to underlying disease. Treatment delay due to toxicity lasting greater than 14 days since the last dose of Venetoclax is also considered a DLT.
Time frame: Up to 28 days (Cycle 1)
Population: Data included are subject to a cutoff date of 05Oct2022.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Febrile neutropenia | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Neutrophil count decreased | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Thrombocytopenia | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Platelet count decreased | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Fatigue | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Dizziness | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Neutropenia | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Dizziness | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Neutropenia | 2 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Thrombocytopenia | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Febrile neutropenia | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Fatigue | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Neutrophil count decreased | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With DLTs of Venetoclax in Combination With Oral AZA (Part 3 Dose Finding Portion) | Platelet count decreased | 1 Participants |
Primary
Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (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 frame: Up to 28 days (Cycle 1)
Population: Data included are subject to a cutoff date of 05Oct2022.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Leukopenia | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Thrombocytopenia | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Neutropenia | 3 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 20 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Platelet count decreased | 1 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Leukopenia | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Neutropenia | 4 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Thrombocytopenia | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 36 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Platelet count decreased | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 50 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Thrombocytopenia | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 50 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Neutropenia | 4 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 50 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Leukopenia | 0 Participants |
| Part 1: Venetoclax 400 mg + Azacitidine 50 mg/m^2 | Number of Participants With Dose-Limiting Toxicities (DLTs) of Venetoclax in Combination With Azacitidine (AZA) (Part 1) | Platelet count decreased | 0 Participants |