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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age12 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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

You cannot join if

• 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

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

enasidenib mesylate. The mesylate salt form of enasidenib, an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity. Upon administration, enasidenib specifically inhibits various mutant forms of IDH2, including the IDH2 variants R140Q, R172S, and R172K, which inhibits the formation of 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH2-expressing tumor cells. IDH2, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by blocking differentiation and the production of the oncometabolite 2HG. NCI Drug Dictionary

Treatments listed in the registry

• Azacitidine (Drug): Given IV or SC
• Enasidenib (Drug): Given PO
• Quality-of-Life Assessment (Other): Ancillary studies

Non Randomized · Parallel · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• questionnaires: Part of the study plan

Main goals

• Incidence of adverse events (Up to 3 years)
• Overall response rate (Up to 3 years)

Other goals

• Event-free survival (EFS)
• Overall survival (OS)
• Anti-tumor activity
• Pharmadynamics (PDn) markers
• Drug exposure levels

Planned enrollment: 63 (estimated).

• M D Anderson Cancer Center, Houston, Texas

Site status as of Oct 30, 2026. Check the live record before contacting a site.

These papers are listed in the registry record. Unless a paper is marked as about this trial, it is background research on the treatment or disease, not results from this study.

• Publication about this trial (to be verified before citing)DiNardo CD, Venugopal S, Lachowiez C, Takahashi K, Loghavi S, Montalban-Bravo G, Wang X, Carraway H, Sekeres M, Sukkur A, Hammond D, Chien K, Maiti A, Masarova L, Sasaki K, Alvarado Y, Kadia T, Short NJ, Daver N, Borthakur G, Ravandi F, Kantarjian HM, Patel B, Dezern A, Roboz G, Garcia-Manero G. Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. Blood Adv. 2023 Jun 13;7(11):2378-2387. doi: 10.1182/bloodadvances.2022008378.

• ClinicalTrials.gov NCT03383575
• NCI Drug Dictionary: C137825

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 3, 2026. Public record; not medical advice.