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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03844815
Recruitment Status : Not yet recruiting
First Posted : February 18, 2019
Last Update Posted : October 9, 2019
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE February 14, 2019
First Posted Date  ICMJE February 18, 2019
Last Update Posted Date October 9, 2019
Estimated Study Start Date  ICMJE April 10, 2020
Estimated Primary Completion Date June 10, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
The rate of dose limiting toxicity (DLT) [ Time Frame: 24 months ]
Determine the rate of subjects who experience a dose limiting toxicity and the maximum tolerable dose
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2019)
  • Levels of toxicity with combination regimen [ Time Frame: 24 months ]
    Levels of toxicity experienced with the combination regimen will be reported using data summaries of adverse events, dose limiting toxicity and other safety parameters.
  • Assessment of Overall Survival [ Time Frame: 24 months ]
    Survival will be measured in months from the date of subject enrollment to the date of death.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Venetoclax in Combination With Decitabine in Subjects With Acute Myeloid Leukemia
Official Title  ICMJE Phase 1 Study of Venetoclax in Combination With Decitabine 10-Day Regimen in Subjects With Acute Myeloid Leukemia
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: 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

  • 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.
Study Arms  ICMJE Experimental: 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

Interventions:
  • Drug: Decitabine
  • Drug: Venetoclax
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2019)
26
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 10, 2024
Estimated Primary Completion Date June 10, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • Phase 2: Dose Expansion Phase 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:

- Key exclusion criteria (apply to both Phase 1 and Phase 2 portions of the study):

  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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Melissa Fridstein 773-702-9885 mfridstein@medicine.bsd.uchicago.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03844815
Other Study ID Numbers  ICMJE IRB18-1498
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE AbbVie
Investigators  ICMJE
Principal Investigator: Olatoyosi Odenike, MD University of Chicago
PRS Account University of Chicago
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP