Decitabine Alone or in Combination With Venetoclax, Gilteritinib, Enasidenib, or Ivosidenib as Maintenance Therapy for the Treatment of Acute Myeloid Leukemia in Remission

• ClinicalTrials.gov Identifier: NCT05010772
• Recruitment Status: Recruiting
• First Posted: August 18, 2021
• Last Update Posted: February 26, 2024
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Tracking Information

• First Submitted Date: August 11, 2021
• First Posted Date: August 18, 2021
• Last Update Posted Date: February 26, 2024
• Actual Study Start Date: October 25, 2021
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 11, 2021)

Incidence of adverse events [ Time Frame: Up to 5 years ]

Safety analyses in general will be descriptive and will be presented in tabular format with the appropriate summary statistics. Adverse events will be tabulated using frequency and percentage by severity and by relations to the treatments for each arm.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 11, 2021)

• Relapse-free survival (RFS) [ Time Frame: From complete remission or complete remission with incomplete count recovery until date of first objective documentation of relapse or death, assessed up to 5 years ]
  The Kaplan-Meier method will be used to estimate RFS.
• Overall survival (OS) [ Time Frame: From date of treatment start until date of death due to any cause, assessed up to 5 years ]
  The Kaplan-Meier method will be used to estimate OS.
• Event-free survival (EFS) [ Time Frame: From treatment start until date of first documented event., assessed up to 5 years ]
  Event will be defined as: confirmed relapse, withdrawal from study due to adverse event, or death due to any cause. The Kaplan-Meier method will be used to estimate EFS.
• Duration of remission [ Time Frame: Up to 5 years ]
  The Kaplan-Meier method will be used to duration of remission.
• Minimal residual disease [ Time Frame: Up to 5 years ]
  The log rank test and Cox proportional hazards model will be used to evaluate the association between the time to event outcomes and status of residual disease.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 11, 2021)

• RFS (Intensive induction cohort) [ Time Frame: Up to 5 years ]
  Kaplan-Meier method will be used to estimate RFS for intensive induction cohort.
• RFS (Lower intensity induction cohort) [ Time Frame: Up to 5 years ]
  Kaplan-Meier method will be used to estimate RFS for lower intensity induction cohort.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Decitabine Alone or in Combination With Venetoclax, Gilteritinib, Enasidenib, or Ivosidenib as Maintenance Therapy for the Treatment of Acute Myeloid Leukemia in Remission
• Official Title: Oral Decitabine-Based Maintenance Therapy in Patients With AML in Remission
• Brief Summary: This phase Ib trial is to find out the side effects and possible benefits of decitabine alone or given together with venetoclax, gilteritinib, enasidenib, or ivosidenib in treating patients with acute myeloid leukemia that is under control (remission). Chemotherapy drugs, such as decitabine, 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. Venetoclax may stop the growth of cancer cells by blocking a protein called Bcl-2 needed for cell growth. Gilteritinib, enasidenib, and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine alone or together with venetoclax, gilteritinib, enasidenib, or ivosidenib may help to control the disease.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess safety of patients with acute myeloid leukemia (AML) treated with decitabine and cedazuridine (oral decitabine)-based combinations as maintenance therapy after achieving remission.

SECONDARY OBJECTIVES:

I. To assess relapse-frees survival (RFS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.

II. To assess overall survival (OS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.

III. To assess event-free survival (EFS) of patients with AML treated with oral decitabine-based combinations as maintenance therapy.

IV. To assess the duration of remission (CRd) of patients with AML treated oral decitabine-based combinations as maintenance therapy.

V. To assess the effects of oral decitabine-based combinations on dynamics of minimal residual disease and their relationship to outcomes.

EXPLORATORY OBJECTIVE:

I. To evaluate RFS in (1) intensive induction cohort and (2) lower intensity induction cohort.

OUTLINE: Patients are assigned to 1 of 5 arms.

ARM A: Patients receive decitabine and cedazuridine orally (PO) once daily (QD) on days 1-3. Treatments repeat every 28 days for up to 4 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive decitabine and cedazuridine PO QD on days 1-3 and venetoclax PO QD on days 1-5. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive decitabine and cedazuridine PO QD on days 1-3 and gilteritinib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM D: Patients receive decitabine and cedazuridine PO QD on days 1-3 and enasidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM E: Patients receive decitabine and cedazuridine PO QD on days 1-3 and ivosidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia

Intervention

• Drug: Decitabine and Cedazuridine
  Given PO
  Other Names:

  • ASTX727
  • C-DEC
  • CDA Inhibitor E7727/Decitabine Combination Agent ASTX727
  • Cedazuridine/Decitabine Combination Agent ASTX727
  • Cedazuridine/Decitabine Tablet
  • DEC-C
  • Inqovi
• Drug: Enasidenib
  Given PO
  Other Names:

  • AG-221
  • CC-90007 Free Base
• Drug: Gilteritinib
  Given PO
  Other Names:

  • ASP-2215
  • ASP2215
• Drug: Ivosidenib
  Given PO
  Other Names:

  • AG-120
  • Tibsovo
• Drug: Venetoclax
  Given PO
  Other Names:

  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta
  • Venclyxto

Study Arms

• Experimental: Arm A (decitabine and cedazuridine)
  Patients receive decitabine and cedazuridine PO QD on days 1-3. Treatments repeat every 28 days for up to 4 weeks in the absence of disease progression or unacceptable toxicity.
  Intervention: Drug: Decitabine and Cedazuridine
• Experimental: Arm B (decitabine and cedazuridine, venetoclax)
  Patients receive decitabine and cedazuridine PO QD on days 1-3 and venetoclax PO QD on days 1-5. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Decitabine and Cedazuridine
  • Drug: Venetoclax
• Experimental: Arm C (decitabine and cedazuridine, gilteritinib)
  Patients receive decitabine and cedazuridine PO QD on days 1-3 and gilteritinib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Decitabine and Cedazuridine
  • Drug: Gilteritinib
• Experimental: Arm D (decitabine and cedazuridine, enasidenib)
  Patients receive decitabine and cedazuridine PO QD on days 1-3 and enasidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Decitabine and Cedazuridine
  • Drug: Enasidenib
• Experimental: Arm E (decitabine and cedazuridine, ivosidenib)
  Patients receive decitabine and cedazuridine PO QD on days 1-3 and ivosidenib PO QD on days 1-28. Treatments repeat every 4 weeks for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  Interventions:

  • Drug: Decitabine and Cedazuridine
  • Drug: Ivosidenib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 11, 2021): 125
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients aged >= 18 years AML who have achieved their FIRST complete response (CR) or complete response with incomplete bone marrow recovery (CRi) and are not immediately candidates for allogeneic stem cell transplant
• Patients who have received intensive therapy (defined as receiving standard or higher dose cytarabine-based therapy) to achieve remission (CR/CRi) should have received remission induction therapy and at least 1 consolidation cycle. These patients are eligible as long as they are not greater than 2 months from their last consolidation therapy and will be designated as COHORT 1 (intensive induction cohort)
• Patients who have received lower intensity therapy (defined as receiving low-dose cytarabine [LDAC] or hypomethylating agent [HMA]-based therapy) to achieve remission should have received at least 2 cycles of lower intensity therapy between the time they have achieved CR/CRi and enrollment on this protocol. They will be designated as COHORT 2 (lower intensity induction cohort)
• For either subgroup (lower or higher intensity), patients who have measurable residual disease may be enrolled on their respective cohort at any time without maximum 'time from consolidation' requirement
• 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/uL
• Platelet count > or = 50 x k/uL

• For females of childbearing age, they may participate if they:

  • Have a negative serum or urine pregnancy test within 10 to 14 days of enrolling
  • Agree to either abstinence or 2 effective contraceptive methods (such as barrier methods or hormonal contraception) 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 French-American-British (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 CNS (central nervous system) 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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tapan M. Kadia, MD; 713-792-7305; tkadia@mdanderson.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05010772
• Other Study ID Numbers: 2021-0237; NCI-2021-08496 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2021-0237 ( Other Identifier: M D Anderson Cancer Center )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: M.D. Anderson Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: M.D. Anderson Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Tapan M Kadia, MD; M.D. Anderson Cancer Center

• PRS Account: M.D. Anderson Cancer Center
• Verification Date: February 2024