Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation

NCT05282459 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: IRB- 62692HEM0056NCI-2022-02837
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1b/2, open-label, single arm study to evaluate if enasidenib is safe and effective in improving anemia and decreasing transfusion needs in subjects diagnosed with lower risk myelodysplastic syndrome (MDS) or nonproliferative chronic myelomonocytic leukemia (CMML) without a mutation in isocitrate dehydrogenase type 2 (IDH2 wildtype). Other objectives include assessment of improvements in platelet production and characterization of the mechanism of action of enasidenib in enhancing endogenous erythropoiesis.

Conditions

Leukemia; Leukemia, Myeloid; Monocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Clinical Response: Hematological Improvement - Erythroid (HI-E)

  Clinical response was assessed as the number of participants achieving a hematological improvement - erythroid (HI-E). Participants were characterized and stratified as nontransfused (NTD), low-transfusion burden (LTB) and high-transfusion burden (HTB), with response defined as follows. * NTD = greater than or equal to 2 consecutive Hb measurements, greater than or equal to 1.5 g/dL for a period of minimum 8 week in an observation period of 16 to 24 week compared to the lowest mean of 2 Hb measurements * LTB = 0 units of RBC transfusions * HTB = greater than or equal to 4 unit or greater than or equal to 50% reduction in RBC transfusions

  16 weeks

Secondary Outcomes (6)

• Related Adverse Events

  12 months

• Time to Hematological Improvement - Erythroid (HI-E)

  16 weeks

• Duration of Hematological Improvement - Erythroid (HI-E)

  16 weeks

• Clinical Response: Hematological Improvement - Platelets (HI-P)

  8 weeks

• Clinical Response: Hematological Improvement - Neutrophils (HI-N)

  8 weeks

Study Arms (1)

Enasidenib mesylat

EXPERIMENTAL

Participants will self administer the enasidenib orally everyday.

Drug: Enasidenib mesylat dose escalation

Interventions

Enasidenib mesylat dose escalation DRUG

Subjects will participate dose escalation with a starting dose of 100 mg. Enasidenib will be self administered orally and daily.

Also known as: (Idhifa, AG 221)

Enasidenib mesylat

Eligibility Criteria

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

You may qualify if:

• Documented diagnosis of
• MDS according to WHO/FAB classification that meets IRSS-R classification of low or intermediate risk disease; and a diagnosed as denovo or secondary MDS (MDS-RS eligible if refractory to or declined luspatercept therapy) OR
• Dysplastic (nonproliferative) CMML with WBC \< 13.0/microL)
• No disease-modifying therapy (HMA, hydrea) within 2 months of starting study
• Age ≥ 18 years of age
• ECOG ≤ 3
• Negative for IDH2 mutation by NGS or multiplex PCR (SNaPshot)
• Has symptomatic anemia defined as hemoglobin \< 10.5 g/dL with any of the following.
• Tachypnea
• Shortness of breath
• Fatigue
• Malaise
• Worsening of cardiovascular function
• Asthenia
• Dyspnea on exertion

You may not qualify if:

• Use of concurrent other erythropoietic agents (including epoetin, darbepoetin), G-CSF within 30 days of study enrollment
• Less than 3 months of life expectancy
• Significant cardiac disease (NYHA Class IV congestive heart failure, or unstable angina or myocardial infarction within the last 6 months
• Harbor IDH2 somatic mutations by NGS or PCR
• Pregnant or breast feeding
• Any uncontrolled bacterial, fungal, viral or other infection.
• No known HIV+ or active hepatitis B or C infection, defined as positive viral load for HBV or HCV or a positive surface antigen (HBsAg) test for hepatitis B.
• Have other causes of anemia: deficiencies in iron, B12, folate; nutritional deficiencies related to gastric surgery, anorexia nervosa, excessive zinc supplementation; gastrointestinal bleed. If nutritional deficiencies can be corrected, potential subject can be rescreened and enrolled if nutritionally replete and still meets eligibility criteria.
• Any other medical history, including laboratory results, deemed by the Principal Investigator likely to interfere with their participation in the study, or to interfere with the interpretation of the results
• Pregnant or breast feeding

Sponsors & Collaborators

• Celgene Corporation: collaborator
• Tian Yi Zhang: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid; Leukemia, Monocytic, Acute

Interventions

enasidenib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Tian Yi Zhang
• Organization: Stanford University

tzhang8@stanford.edu

650-497-6259

Study Officials

• Tian Yi Zhang, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Hematology)

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 16, 2022
• Study Start: January 12, 2022
• Primary Completion: December 3, 2024
• Study Completion: March 3, 2025
• Last Updated: April 17, 2026
• Results First Posted: April 17, 2026

Record last verified: 2026-04

Locations

US (1)