Recruiting

Phase 2

Azacitidine & EnasidenibAzacitidine and Enasidenib in Treating Patients With IDH2-Mutant Myelodysplastic Syndrome

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT03383575

Conditions

Acute Myeloid Leukemia

Blasts 20-30 Percent of Bone Marrow Nucleated Cells

Chronic Myelomonocytic Leukemia

IDH2 Gene Mutation

Myelodysplastic Syndrome With Excess Blasts

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Interventions

Azacitidine

Enasidenib

Quality-of-Life Assessment

Study Details

Brief summary:

This phase II trial studies the side effects and how well azacitidine and enasidenib work in treating patients with IDH2-mutant myelodysplastic syndrome. Azacitidine and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Acute Myeloid Leukemia

Blasts 20-30 Percent of Bone Marrow Nucleated Cells

Chronic Myelomonocytic Leukemia

IDH2 Gene Mutation

Myelodysplastic Syndrome With Excess Blasts

Study ID

NCT03383575

Start date

Jan 17, 2018

Status verified date

Aug, 2026

Completion date

Feb 28, 2027

Anticipated

Primary completion date

Feb 28, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 12+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Signed, informed consent must be obtained prior to any study specific procedures
Subjects with a histologically confirmed diagnosis of MDS, including both MDS and refractory anemia with excess blasts in transformation (RAEB-T) (acute myeloid leukemia \[AML\] with 20-30% blasts and multilineage dysplasia by French-American-British \[FAB\] criteria) by World Health Organization (WHO), and chronic myelomonocytic leukemia (CMML) are eligible
Subjects must have an IDH2 gene mutation (IDH2-R140 or R172) as determined by local laboratory result
(Arm A only): Subject must be hypomethylating agent naive (i.e. prior azacitidine, decitabine, SGI-110 is exclusionary). Receipt of other MDS-directed therapy such as lenalidomide is allowed
(Arm A only): Subjects with high-risk MDS (i.e. International Prostate Symptom Score \[IPSS\] intermediate-2 or high-risk; or revised \[R\]-IPSS high or very-high risk). Patients with intermediate-1 risk by IPSS or intermediate risk by R-IPSS with high-risk molecular features including TP53, ASXL1, EZH2, and/or RUNX1 mutations are also eligible
(Arm B only): Subject must be relapsed or refractory to prior hypomethylating agent therapy, defined as prior receipt of 6 cycles of HMA therapy with failure to attain a response, or relapse after prior response to HMA therapy
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Serum bilirubin =< 2 x the upper limit of normal (ULN) (except for patients with Gilbert's disease)
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x the laboratory ULN
Serum creatinine =< 2 x the ULN
Able to understand and voluntarily sign a written informed consent, and willing and able to comply with protocol requirements
Resolution of all clinically significant treatment-related, non-hematological toxicities, except alopecia, from any previous cancer therapy to =< grade 1 prior to the first dose of study treatment
Female patients of childbearing potential must have a negative serum or urine pregnancy test within 7 days of the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential

Exclusion Criteria:

Any prior or coexisting medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
Subject has received a prior targeted IDH2 inhibitor
Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
Active uncontrolled infection at study enrollment including known diagnosis of human immunodeficiency virus or chronic active hepatitis B or C infection
Clinically significant gastrointestinal conditions or disorders that may interfere with study drug absorption, including prior gastrectomy
Patients with known active central nervous system (CNS) disease, including leptomeningeal involvement
Impaired cardiac function, uncontrolled cardiac arrhythmia, or clinically significant cardiac disease including the following: a) New York Heart Association grade III or IV congestive heart failure, b) myocardial infarction within the last 6 months
Subjects with a corrected QT (QTc) > 480 ms (QTc > 510 msec for subjects with a bundle branch block at baseline
Nursing or pregnant women
Subjects with known hypersensitivity to study drugs or their excipients

Study Design

Enrollment

63 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (enasidenib, azacitidine)

Patients who are HMA-naive receive enasidenib PO QD on days 1-28 and azacitidine IV over 30-60 minutes or SC on days 1-7. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

experimental: Arm II (enasidenib)

Patients relapsed and/or refractory to HMA therapy receive enasidenib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Azacitidine

Given IV or SC

Enasidenib

Given PO

Quality-of-Life Assessment

Ancillary studies

Primary outcome measure

Incidence of adverse events [ Time Frame: Up to 3 years ]
Overall response rate [ Time Frame: Up to 3 years ]

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

Principal Investigator:

Courtney DiNardo

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

Sep 4, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-09-04.