Using enasidenib and azacitidine to treat patients with recurrent or refractory acute myeloid leukemia and IDH2 gene mutation

Phase II Study of the Targeted Mutant IDH2 Inhibitor Enasidenib in Combination With Azacitidine for Relapsed/Refractory AML

Phase 2 Interventional M.D. Anderson Cancer Center · NCT03683433

This study is testing if a combination of two medications, enasidenib and azacitidine, can help people with recurrent or hard-to-treat acute myeloid leukemia that has an IDH2 gene mutation.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment50 (estimated)
Ages18 Years and up
SexAll
SponsorM.D. Anderson Cancer Center Academic / other
Drugs / interventionschemotherapy
Locations1 site (Houston, Texas)
Trial IDNCT03683433 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of enasidenib mesylate in combination with azacitidine for patients suffering from recurrent or refractory acute myeloid leukemia (AML) with an IDH2 gene mutation. The study aims to measure the overall response rate, duration of response, event-free survival, and overall survival among participants. Patients will receive azacitidine either subcutaneously or intravenously for the first week of each treatment cycle, while enasidenib will be administered orally daily. The trial also explores the safety of the combination therapy and the potential for achieving minimal residual disease negativity.

Who should consider this trial

Good fit: Ideal candidates include patients with recurrent or refractory acute myeloid leukemia who have an IDH2 gene mutation and have failed prior therapies.

Not a fit: Patients without an IDH2 gene mutation or those with other types of leukemia not specified in the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat acute myeloid leukemia.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating acute myeloid leukemia, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Patients with AML or biphenotypic or bilineage leukemia (including a myeloid component) who have failed prior therapy. Patients with isolated extramedullary AML are eligible. The World Health Organization (WHO) classification will be used for AML
* Elderly (\> 60 years old) patients with newly diagnosed AML not eligible for intensive chemotherapy are also eligible
* AML patients with prior history of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) regardless of prior therapy received, are eligible at the time of diagnosis of AML
* Subjects must have documented IDH2 gene mutation
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
* Adequate renal function including creatinine \< 2 unless related to the disease
* Total 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
* Provision of written informed consent
* Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the principal investigator (PI). Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
* Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
* Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

Exclusion Criteria:

* Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British \[FAB\] class M3-AML)
* Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
* Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
* Pregnant or breastfeeding

Where this trial is running

Houston, Texas

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Acute Bilineal LeukemiaAcute Biphenotypic LeukemiaChronic Myelomonocytic LeukemiaIDH2 Gene MutationMyelodysplastic SyndromeRecurrent Acute Myeloid LeukemiaRefractory Acute Myeloid Leukemia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.