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

NCT03844815 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB18-1498
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• The rate of dose limiting toxicity (DLT)

  Determine the rate of subjects who experience a dose limiting toxicity and the maximum tolerable dose

  24 months

Secondary Outcomes (2)

• Levels of toxicity with combination regimen

  24 months

• Assessment of Overall Survival

  24 months

Study Arms (1)

Treatment

EXPERIMENTAL

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

Drug: Decitabine; Drug: Venetoclax

Interventions

Decitabine 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

Treatment

Venetoclax 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.

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1: Dose Escalation Phase
• High risk AML, including any of the following:
• Relapsed or refractory disease
• TP53 mutant AML
• 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)
• ECOG performance status 0-2
• Age 18 years or older
• Adequate organ function as defined by all of the following:
• Creatinine clearance ≥30 mL/min, determined by the Cockroft-Gault formula, or measured by a 24 hour urine collection
• 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).
• 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.
• 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.
• Female patients of childbearing potential must have negative results for a pregnancy test
• Patients must be willing to use appropriate contraception

You may not qualify if:

• Concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in this protocol
• Patients suitable for and willing to receive intensive induction chemotherapy
• 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)
• Prior treatment with venetoclax, decitabine, or azacitidine
• Diagnosis of acute promyelocytic leukemia
• Pregnant or breastfeeding patients
• Patient known to be positive for HIV
• Known CNS involvement with AML
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
• Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
• 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.
• An active second cancer that requires treatment within 6 months of study entry
• Cardiac history including the following:
• History of CHF requiring treatment or Ejection Fraction ≤ 50%
• Subject has a cardiovascular disability status of New York Heart Association

Sponsors & Collaborators

• AbbVie: collaborator
• University of Chicago: lead

Study Sites (1)

University Of Chicago Medicine Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Olatoyosi Odenike, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 18, 2019
• Study Start: November 18, 2019
• Primary Completion (Estimated): December 10, 2027
• Study Completion (Estimated): December 10, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)