Study of Venetoclax in Combination With Decitabine in Subjects With Acute Myeloid Leukemia

NCT ID: NCT03844815

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-18
• Study Completion Date: 2025-12-10

Brief Summary

The main purpose of this study is to learn about the safety and tolerability of an experimental drug, Venetoclax, when it is given along with Decitabine in subjects diagnosed with acute myeloid leukemia (AML).

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Cycle 1 of Treatment will be Decitabine days 1-10 plus Venetoclax ramp up on days 1-3 followed by Venetoclax target dose on days 4-21

Cycle 2 of Treatment will be Decitabine days 1-10 plus Venetcolax target dose days 1-21

During maintenance Decitabine on days 1-5 plus Venetoclax days 1-21

Group Type: EXPERIMENTAL

Decitabine

Intervention Type: DRUG

Decitabine will be administered intravenously at a dose of 20mg per day for 10 days during Cycle 1 (28 day cycle)

Decitabine will be administered intravenously at a dose of 20mg per day for 10 days of Cycle 2 (28 day cycle).

Decitabine will be administered intravenously at a dose of 20mg per day for 5 days of each 28 day maintenance cycle

Venetoclax

Intervention Type: DRUG

Venetoclax administered orally on days 1-21 of cycle 1, cycle 2 and maintenance (28 day cycles). Dose levels will be assigned at time of enrollment anywhere from 100mg-400mg. Dose escalation will follow the 3+3 study design.

Interventions

Decitabine

Decitabine will be administered intravenously at a dose of 20mg per day for 10 days during Cycle 1 (28 day cycle)

Decitabine will be administered intravenously at a dose of 20mg per day for 10 days of Cycle 2 (28 day cycle).

Decitabine will be administered intravenously at a dose of 20mg per day for 5 days of each 28 day maintenance cycle

Intervention Type: DRUG

Venetoclax

Venetoclax administered orally on days 1-21 of cycle 1, cycle 2 and maintenance (28 day cycles). Dose levels will be assigned at time of enrollment anywhere from 100mg-400mg. Dose escalation will follow the 3+3 study design.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Phase 1: Dose Escalation Phase

1. High risk AML, including any of the following:

1. Relapsed or refractory disease

2. TP53 mutant AML

3. Adverse risk cytogenetics including any of the following: 3 or more abnormalities; deletions involving chromosomes 5, 7, or 17; abnormalities in chromosome 11 involving MLL; t(6;9); inv(3) or t(3;3)

2. ECOG performance status 0-2

3. Age 18 years or older

4. Adequate organ function as defined by all of the following:

1. Creatinine clearance ≥30 mL/min, determined by the Cockroft-Gault formula, or measured by a 24 hour urine collection

2. AST and ALT ≤3 x ULN and bilirubin ≤1.5 x ULN (unless considered due to Gilbert's syndrome or of non-hepatic origin i.e. leukemic involvement).

5. Patients must be at least 2 weeks from major surgery, radiation therapy, or participation in other investigational trials, and must have recovered from clinically significant toxicities related to these prior treatments.

6. Patients must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the i initiation of any screening or study specific procedures.

7. Female patients of childbearing potential must have negative results for a pregnancy test

8. Patients must be willing to use appropriate contraception

Exclusion Criteria

1. Concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol

2. Patients suitable for and willing to receive intensive induction chemotherapy

3. Use of investigational agents and/or anticancer therapy within 2 weeks of study entry (with the exception of hydroxyurea, which is permitted before and during Cycle 1 of therapy until D10, at the discretion of the investigator)

4. Prior treatment with venetoclax, decitabine, or azacitidine

5. Diagnosis of acute promyelocytic leukemia

6. Pregnant or breastfeeding patients

7. Patient known to be positive for HIV

8. Known CNS involvement with AML

9. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)

2. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.

3. An active second cancer that requires treatment within 6 months of study entry

10. Cardiac history including the following:

1. History of CHF requiring treatment or Ejection Fraction ≤ 50%

2. Subject has a cardiovascular disability status of New York Heart Association

Class > 2, defined as:

i. Cardiac disease in which patients are comfortable at rest but ordinary physical activity ii. Results in fatigue, palpitations, dyspnea, or anginal pain c. Chronic stable angina

11. Treatment with any of the following within 7 days prior to the first dose of study drug:

1. Steroid therapy for anti-neoplastic intent

2. Moderate or strong cytochrome P450 3A (CYP3A) inducers

12. Administration or consumption of any of the following within 3 days prior to the first dose of study drug:

1. Grapefruit or grapefruit products

2. Seville oranges (including marmalade containing Seville oranges)

3. Star fruit

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olatoyosi Odenike, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University Of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

IRB18-1498

Identifier Type: -

Identifier Source: org_study_id