Clinical Trials /

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

NCT03844815

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Venetoclax in Combination With Decitabine in Subjects With Acute Myeloid Leukemia
  • Official Title: Phase 1 Study of Venetoclax in Combination With Decitabine 10-Day Regimen in Subjects With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: IRB18-1498
  • NCT ID: NCT03844815

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
DecitabineTreatment
VenetoclaxTreatment

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalCycle 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
  • Decitabine
  • Venetoclax

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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The rate of dose limiting toxicity (DLT)
Time Frame:24 months
Safety Issue:
Description:Determine the rate of subjects who experience a dose limiting toxicity and the maximum tolerable dose

Secondary Outcome Measures

Measure:Levels of toxicity with combination regimen
Time Frame:24 months
Safety Issue:
Description:Levels of toxicity experienced with the combination regimen will be reported using data summaries of adverse events, dose limiting toxicity and other safety parameters.
Measure:Assessment of Overall Survival
Time Frame:24 months
Safety Issue:
Description:Survival will be measured in months from the date of subject enrollment to the date of death.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Chicago

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