Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT04062266
Recruitment Status : Recruiting
First Posted : August 20, 2019
Last Update Posted : October 4, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 16, 2019
First Posted Date  ICMJE August 20, 2019
Last Update Posted Date October 4, 2019
Actual Study Start Date  ICMJE September 13, 2019
Estimated Primary Completion Date October 31, 2030   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
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 ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04062266 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2019)
  • Incidence of toxicity [ Time Frame: Up to 10 years ]
    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).
  • 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 ]
    Distribution assessed using Kaplan-Meier method.
  • 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 ]
    Distribution assessed using Kaplan-Meier method.
  • 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 ]
    Distribution assessed using Kaplan-Meier method.
  • 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 ]
    Distribution assessed using Kaplan-Meier method.
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 Azacitidine and Venetoclax in Treating Patients With High Risk Acute Myeloid Leukemia in Remission
Official Title  ICMJE Phase II Study of 5-Azacytidine (AZA) + Venetoclax as Maintenance Therapy in Patients With High Risk AML in Remission
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Azacitidine
    Given SC or IV
    Other Names:
    • 5 AZC
    • 5-AC
    • 5-Azacytidine
    • 5-AZC
    • Azacytidine
    • Azacytidine, 5-
    • Ladakamycin
    • Mylosar
    • U-18496
    • Vidaza
  • Drug: Venetoclax
    Given PO
    Other Names:
    • ABT-0199
    • ABT-199
    • ABT199
    • GDC-0199
    • RG7601
    • Venclexta
    • Venclyxto
Study Arms  ICMJE Experimental: Treatment (azacytidine, venetoclax)
Patients 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.
Interventions:
  • Drug: Azacitidine
  • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2019)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2030
Estimated Primary Completion Date October 31, 2030   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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: Tapan M. Kadia 713-563-3534 tkadia@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04062266
Other Study ID Numbers  ICMJE 2019-0226
NCI-2019-04987 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2019-0226 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
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 M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date October 2019

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