Clinical Trials /

Venetoclax and Azacitidine for Non-Elderly Adult Patients With Acute Myeloid Leukemia

NCT03573024

Description:

This study aims to treat non-elderly adult patients, who were previously untreated for acute myeloid leukemia, using venetoclax and azacitidine.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Venetoclax and Azacitidine for Non-Elderly Adult Patients With Acute Myeloid Leukemia
  • Official Title: Safety and Efficacy of Venetoclax and Azacitidine for Newly Diagnosed Non-Elderly Adult Patients (Aged 18-59) With Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: 18-0709.cc
  • NCT ID: NCT03573024

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
AzacitidineAzacitidine and Venetoclax
VenetoclaxAzacitidine and Venetoclax

Purpose

This study aims to treat non-elderly adult patients, who were previously untreated for acute myeloid leukemia, using venetoclax and azacitidine.

Detailed Description

      This is a phase II study that seeks to treat patients ages 18-59 who have acute myeloid
      leukemia but have never been treated before. It will use venetoclax and azacitidine, and
      patients can receive up to four cycles of this medication. Depending on the level of
      recovery, patients will either be forced to come off study or have the option to continue the
      medication, receive maintenance therapy, or pursue an allogeneic stem cell transplant.
    

Trial Arms

NameTypeDescriptionInterventions
Azacitidine and VenetoclaxExperimentalAzacitidine will be given intravenously for 7 days. Venetoclax will be given orally. The patient will start out with 100mg and progress to 600mg. Once 600mg is reached, the patient will stay at this dose until the 28 day cycle is finished.
  • Azacitidine
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

        A subject will be eligible for study participation if he/she meets the following criteria
        within 28 days prior to the first day of therapy (bone marrow biopsy can be performed 28
        days prior to the first day of therapy). Historical records are permitted per Investigator
        discretion.

          1. Subject must have confirmation of non-APL and AML by WHO criteria45

          2. Subject must have received no prior treatment for AML

          3. Age ≥18 years, ≤59 years

          4. Without clinical signs of active central nervous system disease

          5. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of
             ≤2

          6. Subject must have adequate renal function as demonstrated by a calculated creatinine
             clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine
             clearance or by the Cockcroft Gault formula

          7. Subject must have adequate liver function as demonstrated by:

               -  aspartate aminotransferase (AST) ≤ 3.0 × ULN*

               -  alanine aminotransferase (ALT) ≤ 3.0 × ULN*

               -  bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome* * Unless considered due
                  to leukemic organ involvement

          8. Non-sterile male subjects must use contraceptive methods with partner(s) prior to
             beginning study drug administration and continuing up to 90 days after the last dose
             of study drug. Male subjects must agree to refrain from sperm donation from initial
             study drug administration until 90 days after the last dose of study drug.

          9. Female subjects who are pre-menopausal and have not had a hysterectomy or oophorectomy
             must agree to use two reliable forms of contraception simultaneously or to practice
             complete abstinence from heterosexual intercourse during the following time periods
             related to this study: 1) for at least 28 days before starting therapy; 2) throughout
             the entire duration of treatment; 3) during dose interruptions; and 4) for at least 90
             days after discontinuation of therapy (last dose of study drug).

         10. Subject must voluntarily sign and date an informed consent, approved by an
             Institutional Review Board (IRB), prior to the initiation of any research directed
             screening procedures.

         11. Subject must have adverse risk disease as defined by the European LeukemiaNet46
             (Appendix B) 5.3.2 Exclusion Criteria

        A subject will not be eligible for study participation if he/she meets any of the following
        criteria:

          1. Subject has received disease modifying treatment for myelodysplastic syndrome (MDS) or
             AML. ATRA given for clinical suspicion of APL will not be exclusionary and no washout
             will be required in this scenario.

          2. Subject is known to be positive for HIV. HIV testing is not required.

          3. Subject is known to be positive for hepatitis B or C infection with the exception of
             those with an undetectable viral load. Hepatitis B or C testing is not required and
             subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, anti-HBs+
             and anti-HBc-) may participate

          4. Subject has received within 7 days prior to the first dose of study drug:steroid
             therapy for anti-neoplastic intent; strong and moderate CYP3A inhibitors; strong and
             moderate CYP3A inducers.

          5. Subject is informed that consumption of the following fruits is prohibited 3 days
             prior to the initiation of study treatment and throughout participation: grapefruit,
             grapefruit products, Seville oranges (including marmalade containing Seville oranges)
             or Star fruit.

          6. Subject has any history of clinically significant condition(s) that in the opinion of
             the investigator would adversely affect his/her participating in this study including,
             but not limited to:

               -  New York Heart Association heart failure > class 2

               -  Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic,
                  cardiovascular disease, or bleeding disorder independent of leukemia

          7. Subject has a malabsorption syndrome or other condition that precludes enteral route
             of administration

          8. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral,
             bacterial or fungal)

          9. Subject has a history of other malignancies prior to study entry, with the exception
             of:

               -  Adequately treated in situ carcinoma of the breast or cervix uteri

               -  Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin

               -  Prostate cancer with no plans for therapy of any kind

               -  Previous malignancy confined and surgically resected (or treated with other
                  modalities) with curative intent.

         10. Subject has a white blood cell count >25 × 10^9/L or absolute blast count of >50
             10^9/L. Hydroxyurea and leukapheresis are permitted, if clinically indicated.

         11. Patients willing to receive intensive induction chemotherapy

         12. Pregnant and breastfeeding females.
      
Maximum Eligible Age:59 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response Rate, measured by the European Leukemia Net definition: (CRMRD-+CR+CRi+MLFS)
Time Frame:Study start date to study end date, or death, whichever comes first, up to 4 years
Safety Issue:
Description:The (CRMRD-+CR+CRi+MLFS) shows non-inferiority of venetoclax with azacitidine when compared with historical controls who received induction chemotherapy.

Secondary Outcome Measures

Measure:Incidence of Minimal Residual Disease (MRD) Negative Responses
Time Frame:Study start date to study end date, or death, whichever comes first, up to 4 years
Safety Issue:
Description:Number of new cases of Complete Remission, Complete Remission with Incomplete Blood Count Recovery, or Morphologic Leukemia Free State. This will be measure by multi-dimensional flow cytometry with a sensitivity to 0.1%.
Measure:Remission Duration
Time Frame:Study start date to study end date, or death, whichever comes first, up to 4 years
Safety Issue:
Description:Remission Duration will be defined as the length of time a patient does not display leukemic blasts or extramedullary disease
Measure:One Year Event Free Survival
Time Frame:Study start date to study end date, or death, whichever comes first, up to 4 years
Safety Issue:
Description:Determined using Kaplan Meier survival analysis methods with 95% confidence intervals.
Measure:Overall Survival
Time Frame:Study start date to study end date, or death, whichever comes first, up to 4 years
Safety Issue:
Description:Overall Survival will be defined as the time from administration of the initial doses until death from any cause. Determined using Kaplan Meier survival analysis methods with 95% confidence intervals.
Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame:Study start date to study end date, or death, whichever comes first, up to 4 years
Safety Issue:
Description:Safety and tolerability analysis of azacitidine and venetoclax will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 and relationship to study drug.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • Venetoclax
  • Azacitidine
  • Non-Elderly
  • Previously Untreated

Last Updated

February 11, 2020