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Venetoclax in Combination with Decitabine for the Treatment of High-Risk Acute Myeloid Leukemia

Trial Status: Active

This phase I trial evaluates the best dose and side effects of venetoclax when given in combination with decitabine in treating patients with acute myeloid leukemia. Venetoclax may kill or stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell growth and survival. Decitabine belongs to a class of anti-cancer drugs known as DNA methyltransferase (DNMT) inhibitors, which change how diseased cells in the blood and bone marrow grow and multiply. Giving venetoclax in combination with decitabine may help treat patients with acute myeloid leukemia.

Inclusion Criteria

  • 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)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Age >= 18 years old
  • Creatinine clearance >= 30 mL/min, determined by the Cockcroft-Gault formula, or measured by a 24 hour urine collection
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x upper limit of normal (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 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
  • During the phase 2 portion of the study, the subject population will be limited to patients with previously untreated AML with a mutation in TP53. All other inclusion criteria described above will apply

Exclusion Criteria

  • 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 day 10 (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 human immunodeficiency virus (HIV)
  • Known central nervous system (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 virus (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 congestive heart failure (CHF) requiring treatment or ejection fraction =< 50% * Subject has a cardiovascular disability status of New York Heart Association Class > 2, defined as: ** Cardiac disease in which patients are comfortable at rest but ordinary physical activity ** Results in fatigue, palpitations, dyspnea, or anginal pain * Chronic stable angina
  • Treatment with any of the following within 7 days prior to the first dose of study drug: * Steroid therapy for anti-neoplastic intent * Moderate or strong cytochrome P450 3A (CYP3A) inducers
  • Administration or consumption of any of the following within 3 days prior to the first dose of study drug: * Grapefruit or grapefruit products * Seville oranges (including marmalade containing Seville oranges) * Star fruit


University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Olatoyosi Muinat Odenike
Phone: 773-702-3354


I. To determine the maximum tolerated dose (MTD) of venetoclax when combined with a decitabine 10-day regimen in patients with high risk acute myeloid leukemia (AML).


I. To assess the efficacy of decitabine 10 day regimen when combined with venetoclax in patients with previously untreated AML with TP53 mutation based on a determination of the following in the dose expansion phase of the study:

Ia. Overall survival.

Ib. Overall response rate--complete remission (CR), complete remission with incomplete blood count recovery (CRi), and partial remission (PR)--with the combination of venetoclax plus 10 days of decitabine in this patient population.

Ic. Time to response and duration of response (disease free survival among responders).


I. To describe the proportion of patients who went on to receive an allogeneic hematopoietic stem cell transplant (alloHCT).

II. To assess the proportion of participants attaining minimal residual disease (MRD) negative status.

III. To assess ex vivo assays that may serve as predictive biomarkers of response to the combination (i.e. BH3 profiling to predict apoptotic response to BCL2 inhibition).

IV. To assess baseline 5hmC signature as a predictive biomarker of response.

OUTLINE: This is a dose-escalation study of venetoclax followed by a dose-expansion study.

INDUCTION: Patients receive venetoclax orally (PO) once daily (QD) on days 1-21, and decitabine intravenously (IV) over 1 hour daily on days 1-10. Treatment repeats every 28 days for 2 cycles in the absence of disease progression and unacceptable toxicity. Patients who achieve CR, CRi, or any clinical benefit proceed to maintenance therapy. Patients without pathologic response or benefit may receive another 1 or 2 cycles of induction therapy.

MAINTENANCE: Patients receive venetoclax PO QD on days 1-21, and decitabine IV over 1 hour daily on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then periodically up to 3 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Olatoyosi Muinat Odenike

  • Primary ID IRB18-1498
  • Secondary IDs NCI-2020-13886
  • ID NCT03844815