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

NCT05010772 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0237NCI-2021-08496
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  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.

  Up to 5 years

Secondary Outcomes (5)

• Relapse-free survival (RFS)

  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

• Overall survival (OS)

  From date of treatment start until date of death due to any cause, assessed up to 5 years

• Event-free survival (EFS)

  From treatment start until date of first documented event., assessed up to 5 years

• Duration of remission

  Up to 5 years

• Minimal residual disease

  Up to 5 years

Other Outcomes (2)

• RFS (Intensive induction cohort)

  Up to 5 years

• RFS (Lower intensity induction cohort)

  Up to 5 years

Study Arms (5)

Arm A (decitabine and cedazuridine)

EXPERIMENTAL

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.

Drug: Decitabine and Cedazuridine

Arm B (decitabine and cedazuridine, venetoclax)

EXPERIMENTAL

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.

Drug: Decitabine and Cedazuridine; Drug: Venetoclax

Arm C (decitabine and cedazuridine, gilteritinib)

EXPERIMENTAL

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.

Drug: Decitabine and Cedazuridine; Drug: Gilteritinib

Arm D (decitabine and cedazuridine, enasidenib)

EXPERIMENTAL

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.

Drug: Decitabine and Cedazuridine; Drug: Enasidenib

Arm E (decitabine and cedazuridine, ivosidenib)

EXPERIMENTAL

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.

Drug: Decitabine and Cedazuridine; Drug: Ivosidenib

Interventions

Decitabine and Cedazuridine DRUG

Given PO

Also known as: ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inqovi

Arm A (decitabine and cedazuridine); Arm B (decitabine and cedazuridine, venetoclax); Arm C (decitabine and cedazuridine, gilteritinib); Arm D (decitabine and cedazuridine, enasidenib); Arm E (decitabine and cedazuridine, ivosidenib)

Enasidenib DRUG

Given PO

Also known as: AG-221, CC-90007 Free Base

Arm D (decitabine and cedazuridine, enasidenib)

Gilteritinib DRUG

Given PO

Also known as: ASP-2215, ASP2215

Arm C (decitabine and cedazuridine, gilteritinib)

Ivosidenib DRUG

Given PO

Also known as: AG-120, Tibsovo

Arm E (decitabine and cedazuridine, ivosidenib)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Arm B (decitabine and cedazuridine, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

decitabine and cedazuridine drug combination; enasidenib; gilteritinib; ivosidenib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Tapan M Kadia, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tapan M. Kadia, MD

CONTACT

713-792-7305; tkadia@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2021
• First Posted: August 18, 2021
• Study Start: October 25, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (1)