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Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation
Trial ID: NCT05282459
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.
A Phase Ib/II, Single Center, Open-Label, Safety and Efficacy Study to Improve Anemia in Subjects on Enasidenib With Lower Risk Myelodysplastic Syndrome and Non-proliferative Chronic Myelomonocytic Leukemia Without an IDH2 Mutation
1. 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)
2. No disease-modifying therapy (HMA, hydrea) within 2 months of starting study
3. Age ≥ 18 years of age
4. ECOG ≤ 3
5. Negative for IDH2 mutation by NGS or multiplex PCR (SNaPshot)
6. Has symptomatic anemia defined as hemoglobin < 10.5 g/dL with any of the following.
- Shortness of breath
- Worsening of cardiovascular function
- Dyspnea on exertion
- Other subject symptoms the subject reports as being associated with being anemic.
7. Stated willingness to comply with all study procedures and availability for the
duration of the study
8. Ability to take oral medication and be willing to adhere to the medication regimen.
9. Females of reproductive potential need to either commit to true abstinence from
heterosexual contact or agree to use, and be able to comply with highly effective
contraception without interruption, 28 days prior to starting enasidenib, during the
study therapy, and for 30 days after last dose of enasidenib
10. For males of reproductive potential: agreement to use of condoms
11. Adequate organ function defined as:
- Hepatic function: total bilirubin <1.5 x ULN (unless attributable to Gilbert's
disease), AST or ALT < 3x ULN
- Renal function: creatinine clearance > 30 mL/minute, calculated by
12. Ability to understand and the willingness to sign the IRB approved informed consent
13. Women of childbearing potential must have negative urine or serum pregnancy test
1. Use of concurrent other erythropoietic agents (including epoetin, darbepoetin), G-CSF
within 30 days of study enrollment
2. Less than 3 months of life expectancy
3. Significant cardiac disease (NYHA Class IV congestive heart failure, or unstable
angina or myocardial infarction within the last 6 months
4. Harbor IDH2 somatic mutations by NGS or PCR
5. Pregnant or breast feeding
6. Any uncontrolled bacterial, fungal, viral or other infection.
7. 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.
8. 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.
9. 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
10. Pregnant or breast feeding
drug: Enasidenib mesylat dose escalation