Recruiting

Phase 1

Phase 2

ASTX727, Venetoclax, Ivosidenib, EnasidenibDecitabine/Cedazuridine and Venetoclax in Combination With Ivosidenib or Enasidenib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT04774393

Conditions

Acute Myeloid Leukemia

Recurrent Acute Myeloid Leukemia

Refractory Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Decitabine and Cedazuridine

Enasidenib

Ivosidenib

Venetoclax

Study Details

Brief summary:

This phase Ib/II trials studies the side effects of decitabine/cedazuridine (ASTX727) and venetoclax in combination with ivosidenib or enasidenib, and how well they work in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). ASTX727 is the combination of a fixed dose of 2 drugs, cedazuridine and decitabine. Cedazuridine may slow down how fast decitabine is broken down by the body, and decitabine may block abnormal cells or cancer cells from growing. Venetoclax may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Enasidenib and ivosidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine/cedazuridine and venetoclax in combination with ivosidenib or enasidenib may help control acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Recurrent Acute Myeloid Leukemia

Refractory Acute Myeloid Leukemia

Study ID

NCT04774393

Start date

May 24, 2021

Status verified date

May, 2026

Completion date

Nov 29, 2027

Anticipated

Primary completion date

Nov 29, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Patients with a diagnosis of relapsed or refractory acute myeloid leukemia (AML) (including biphenotypic or bilineage leukemia including a myeloid component or isolated extramedullary AML); OR
Patients (> 60 year old) with newly diagnosed AML not eligible for intensive chemotherapy are also eligible
To be considered not eligible for intensive chemotherapy, participants must be defined by the following: Age 75 years or older, or Age 18 to 74 years with at least one of the following comorbidities:
Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina).
Severe pulmonary disorder (eg, DLCO ≤65% or forced expiratory volume in 1 second \[FEV1\] ≤65%).
Creatinine clearance ≥30 mL/min to <45 mL/min.
Moderate hepatic impairment with total bilirubin >1.5 to ≤3.0 × upper limit of normal (ULN)
ECOG performance status of 2 or 3
Age >= 18 years
Subjects must have documented IDH1 or IDH2 gene mutation
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Adequate renal function including creatinine < 2 unless related to the disease
Direct bilirubin < 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5 x ULN will be considered eligible)
In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 7 days for cytotoxic or non-cytotoxic (immunotherapy agent(s). Oral hydroxyurea and/or cytarabine (up to 2 g/m\^2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principle investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
Male subjects who are sexually active with a women of childbearing potential (WOCBP) and who have not had vasectomies must be willing to use a barrier method of contraception and refrain from sperm donation from initial study drug until 90 days after last dose of study drug
Willing and able to provide informed consent

Exclusion Criteria:

Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
Patients with any concurrent uncontrolled clinically significant medical condition including life-threatening severe infection, or psychiatric illness, which could place the patient at unacceptable risk of study treatment
Patients with active graft-versus-host-disease (GVHD) status post stem cell transplant (patients without active GVHD on chronic suppressive immunosuppression and/or phototherapy for chronic skin GVHD are permitted after discussion with the PI)
Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications
Corrected QT (QTc) interval using Fridericia's formula (QTcF) >= 450 msec. Bundle branch block and prolonged QTc interval are permitted after discussion with the PI
Known active hepatitis B (HBV) or hepatitis C (HCV) infection or known human immunodeficiency virus (HIV) infection
Subject has a white blood cell count > 25 x 10\^9/L. (Note: Hydroxyurea is permitted to meet this criterion)
Nursing women, women of childbearing potential (WOCBP) with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception

Appropriate highly effective method(s) of contraception include oral or injectable hormonal birth control, intrauterine device (IUD), and double barrier methods (for example a condom in combination with a spermicide)

Study Design

Enrollment

84 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (decitabine/cedazuridine, venetoclax, ivosidenib)

Patients receive decitabine/cedazuridine PO daily on days 1-5, venetoclax PO daily on days 1-14, and ivosidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

experimental: Arm B (decitabine/cedazuridine, venetoclax, enasidenib)

Patients receive decitabine/cedazuridine PO daily on days 1-5, venetoclax PO daily on days 1-14, and enasidenib PO daily on days 1-28. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Interventions

Decitabine and Cedazuridine

Given PO

Enasidenib

Given PO

Ivosidenib

Given PO

Venetoclax

Given PO

Primary outcome measure

Dose limiting toxicity (Phase Ib) [ Time Frame: Up to 1 cycle (1 cycle = 28 days) ]
Overall response rate (ORR) (Phase II) [ Time Frame: Within 4 months of treatment ]
Incidence of adverse events (Phase II) [ Time Frame: Within 4 months of treatment ]

Central Contacts and Locations

Central contacts

Courtney DiNardo, MD

713-794-1141 cdinardo@mdanderson.org

Locations

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Courtney DiNardo

713-794-1141 cdinardo@mdanderson.org

Principal Investigator:

Courtney DiNardo

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

May 20, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-05-20.