Clinical Trials /

Azacitidine and Venetoclax in Treating Patients With High Risk Acute Myeloid Leukemia in Remission

NCT04062266

Description:

This phase II trial studies how well azacitidine and venetoclax work in treating patients with high risk acute myeloid leukemia that is in remission. Drugs used in chemotherapy, such as azacitidine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Azacitidine and Venetoclax in Treating Patients With High Risk Acute Myeloid Leukemia in Remission
  • Official Title: Phase II Study of 5-Azacytidine (AZA) + Venetoclax as Maintenance Therapy in Patients With High Risk AML in Remission

Clinical Trial IDs

  • ORG STUDY ID: 2019-0226
  • SECONDARY ID: NCI-2019-04987
  • SECONDARY ID: 2019-0226
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04062266

Conditions

  • Acute Myeloid Leukemia in Remission
  • FLT3 Gene Mutation
  • Hematologic and Lymphocytic Disorder
  • High Risk Acute Myeloid Leukemia
  • Minimal Residual Disease Persistence
  • Therapy-Related Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Azacitidine5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, VidazaTreatment (azacytidine, venetoclax)
VenetoclaxABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, VenclyxtoTreatment (azacytidine, venetoclax)

Purpose

This phase II trial studies how well azacitidine and venetoclax work in treating patients with high risk acute myeloid leukemia that is in remission. Drugs used in chemotherapy, such as azacitidine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess relapse-free survival (RFS) of patients (pts) with acute myeloid leukemia (AML)
      treated with 5-azacytidine (azacitidine; AZA) combined with venetoclax (VEN) as maintenance
      therapy after achieving remission.

      SECONDARY OBJECTIVES:

      I. To assess modified RFS of pts with AML treated with 5-azacytidine combined with venetoclax
      as maintenance therapy.

      II. To assess overall survival (OS) of pts with AML treated with 5-azacytidine combined with
      venetoclax as maintenance therapy.

      III. To assess event-free survival (EFS) of pts with AML treated with 5-azacytidine combined
      with venetoclax as maintenance therapy.

      IV. To assess the duration of remission (CRd) of pts with AML treated 5-azacytidine combined
      with venetoclax as maintenance therapy.

      V. To assess toxicity and safety of 5-azacytidine combined with venetoclax as maintenance
      therapy in pts with AML.

      VI. To assess the effects of 5-azacytidine combined with venetoclax on dynamics of minimal
      residual disease (MRD) and their relationship to outcomes.

      OUTLINE:

      Patients receive azacitidine subcutaneously (SC) or intravenously (IV) over 1 hour daily on
      days 1-5, and venetoclax orally (PO) daily on days 1-14. Treatment repeats every 28 days for
      up to 24 cycles in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 6-12
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (azacytidine, venetoclax)ExperimentalPatients receive azacitidine SC or IV over 1 hour daily on days 1-5, and venetoclax PO daily on days 1-14. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  • Azacitidine
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with high risk AML who have achieved their FIRST complete remission (CR) or
             complete remission with incomplete count recovery (CRi) within 12 months of enrollment
             and are not immediately candidates for allogeneic stem cell transplant.

          -  Patients in their FIRST CR or CRi may be eligible for enrollment only if they have a
             high risk feature, including, but not limited to: adverse karyotype, FLT3 mutation,
             history of antecedent hematologic disorder (AHD), presence of dysplasia in the bone
             marrow, therapy-related AML, history of requiring more than 1 cycle of intensive
             induction chemotherapy to achieve first remission, or presence of persistent minimal
             residual disease (detected by cytogenetics, molecular markers, or flow cytometry) at
             any point after initial induction cycle. Patients aged > or = 18 years with AML who
             have achieved a SECOND CR or CRi within 12 months of enrollment and are not
             immediately candidates for allogeneic stem cell transplant are also eligible.

          -  Patients should have received induction chemotherapy for AML and at least 1
             consolidation.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of < or = 3.

          -  Serum total bilirubin < or = to 1.5 x the upper limit of normal (ULN).

          -  Serum creatinine < or = to 2.5 x ULN.

          -  Absolute neutrophil count (ANC) > 0.5 x k/mcgL.

          -  Platelet count > or = 30 x k/mgcL.

          -  For females of childbearing age, they may participate if they: a) Have a negative
             serum or urine pregnancy test within 10 to 14 days of enrolling; b) Agree to either
             abstinence or 2 effective contraceptive methods throughout the treatment period and up
             to 30 days after discontinuing treatment.

          -  For male patients with a female partner of childbearing age, they may participate if
             they agree to either abstinence or 2 effective contraceptive methods throughout the
             treatment period and up to 30 days after discontinuing treatment.

          -  Ability to understand and sign informed consent.

        Exclusion Criteria:

          -  Diagnosis of acute promyelocytic leukemia (APL), AML - M3 by FAB classification based
             on morphology, immunophenotype, molecular, or cytogenetics studies.

          -  Diagnosis of AML associated t(15;17) or APL variant. Patients with t(9;22) are also
             ineligible unless they are unable or unwilling to receive therapy with a tyrosine
             kinase inhibitor.

          -  Uncontrolled intercurrent illness including, but not limited to active uncontrolled
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients with active central nervous system (CNS) disease.

          -  Patients with documented hypersensitivity to any components of the study program.

          -  Females who are pregnant or lactating or intending to become pregnant during the
             study.

          -  Patients with history of extramedullary AML, except for CNS involvement that is
             currently controlled, will not be eligible for enrollment.

          -  Patient should be removed from current trial if they wish to participate and get
             treatment on another trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Relapse-free survival (RFS)
Time Frame:From date of complete remission (CR) or complete remission with incomplete count recovery (CRi), assessed for up to 10 years
Safety Issue:
Description:The study will be continuously monitored for the primary endpoint, RFS, using the method of Thall, Wooten, and Tannir (2005). Will also summarize the posterior distribution of lambda-E (i.e., median RFS) assuming posterior mean and 95% credible interval.

Secondary Outcome Measures

Measure:Incidence of toxicity
Time Frame:Up to 10 years
Safety Issue:
Description:Toxicities are defined as any treatment -related clinically significant grade 3 or 4 non-hematologic adverse events occurred during cycles 1-2 of the trial. Will continuously monitor treatment-related toxicities using the Bayesian approach of Thall, Simon, Estey (1995).
Measure:Modified RFS
Time Frame:Time from enrollment on study until date of first objective documentation of relapse or death, assessed for up to 10 years
Safety Issue:
Description:Distribution assessed using Kaplan-Meier method.
Measure:Overall survival (OS)
Time Frame:From the start of study treatment until date of death due to any cause, assessed for up to 10 years
Safety Issue:
Description:Distribution assessed using Kaplan-Meier method.
Measure:Event free survival (EFS)
Time Frame:From the start of study treatment until date of first confirmed relapse, withdrawal from study due to adverse event, or death due to any cause, assessed for up to 10 years
Safety Issue:
Description:Distribution assessed using Kaplan-Meier method.
Measure:Complete remission duration (CRd)
Time Frame:Time from CR or CRi until date of first objective documentation of confirmed relapse, assessed for up to 10 years
Safety Issue:
Description:Distribution assessed using Kaplan-Meier method.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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