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

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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

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.

Condition or disease Intervention/treatment Phase
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 Drug: Azacitidine Drug: Venetoclax Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of 5-Azacytidine (AZA) + Venetoclax as Maintenance Therapy in Patients With High Risk AML in Remission
Actual Study Start Date : September 13, 2019
Estimated Primary Completion Date : October 31, 2030
Estimated Study Completion Date : October 31, 2030


Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04062266


Contacts
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Contact: Tapan M. Kadia 713-563-3534 tkadia@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Tapan M. Kadia    713-563-3534      
Principal Investigator: Tapan M. Kadia         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Genentech, Inc.
Investigators
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Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04062266     History of Changes
Other Study ID Numbers: 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 )
First Posted: August 20, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Venetoclax
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasm, Residual
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Neoplastic Processes
Pathologic Processes
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors