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

Sponsor
Tian Yi Zhang (Other)
Overall Status
Recruiting
CT.gov ID
NCT05282459
Collaborator
Celgene Corporation (Industry)
48
1
1
23.6
2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Enasidenib mesylat dose escalation
Phase 1/Phase 2

Detailed Description

Primary Objective(s)- To determine the efficacy (response rate) of enasidenib in improving anemia and decreasing RBC transfusion dependence.

Secondary Objective(s)- To determine the tolerability, safety and durability of the erythroid response and identify laboratory parameters as clinical markers of response.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
48 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Supportive Care
Official Title:
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
Actual Study Start Date :
Jan 12, 2022
Anticipated Primary Completion Date :
Jan 1, 2024
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Enasidenib mesylat

Participants will self administer the enasidenib orally everyday.

Drug: Enasidenib mesylat dose escalation
Subjects will participate dose escalation with a starting dose of 100 mg. Enasidenib will be self administered orally and daily.
Other Names:
  • (Idhifa, AG 221)
  • Outcome Measures

    Primary Outcome Measures

    1. Clinical Response: Hematological Improvement - Erythroid (HI-E) [16 weeks]

      Clinical response was assessed as the number of participants achieving a hematological improvement - erythroid (HI-E). Participants will be 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 The outcome will be reported as the number of participants that achieve the response, a number without dispersion.

    2. Related Adverse Events [12 months]

      Toxicity will be assessed as the number of related non serious adverse events and related serious adverse events (SAEs) reported for the 12 cycle treatment period plus follow up. The outcome will be reported as numbers without dispersion.

    3. Time to Hematological Improvement - Erythroid (HI-E) [16 weeks.]

      Time to hematological improvement - erythroid (HI-E) will be assessed as the time from first dose of enasidenib to the first observed hemoglobin response. Participants will be 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 The outcome will be reported as the number of participants that achieve the response, a number without dispersion.

    4. Duration of Hematological Improvement - Erythroid (HI-E) [16 weeks.]

      Duration of Hematological Improvement - Erythroid (HI-E) will be assessed as the time from recorded response to loss of response. Participants will be 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 The outcome will be reported as the number of participants that achieve the response, a number without dispersion.

    5. Clinical Response: Hematological Improvement - Platelets (HI-P) [8 weeks]

      Clinical response for platelets was assessed as the number of participants achieving a hematological improvement - platelets (HI-P). Participants will be characterized and stratified as platelets < or ≥ 20 x 10^9/L, with response defined as follows. < 20 x 10^9/L = increase in platelets from < 20 x 10^9/L to > 20 x 10^9/L AND by ≥ 100% ≥ 20 x 10^9/L = absolute increase in platelets of 30 x 10^9/L The outcome will be reported as the number of participants that achieve the response, a number without dispersion.

    6. Clinical Response: Hematological Improvement - Neutrophils (HI-N) [8 weeks]

      Clinical response for neutrophils was assessed as the number of participants achieving a hematological improvement - neutrophils (HI-N). Response defined as an absolute increase in neutrophils > 0.5 x 10^9/L that is also an increase of ≥ 100%. The outcome will be reported as the number of participants that achieve the response, a number without dispersion.

    7. Red Blood Cell (RBC) transfusion independence (RBC TI) [12 months]

      Clinical response for red blood cells was assessed as the number of participants who were transfusion dependent that achieve red blood cell (RBC) transfusion independence (RBC TI) for for 8 weeks or longer. The outcome will be reported as the number of participants that achieve the response, a number without dispersion.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Documented diagnosis of 1) MDS according to WHO/FAB classification that meets IRSS-R classification of very low or lower risk disease; and a diagnosed as de novo or secondary MDS (MDS RS eligible if refractory to or declined luspatercept therapy).

    OR 2) Dysplastic (nonproliferative) CMML with WBC <13.0/microL)

    1. No disease modifying therapy (HMA, hydrea) within 2 months of starting study

    2. Age ≥ 18 years of age

    3. ECOG ≤ 3

    4. Negative for IDH2 mutation by NGS or multiplex PCR (SNaPshot)

    5. Has symptomatic anemia defined as hemoglobin < 10.0 g/dL with any of the following.

    oTachypnea oShortness of breath oFatigue oMalaise oWorsening of cardiovascaular function oAsthenia oDyspnea on exertion oAngina oOther subject symptoms the subject reports as being associated with being anemic.

    1. Stated willingness to comply with all study procedures and availability for the duration of the study

    2. Ability to take oral medication and be willing to adhere to the medication regimen.

    3. 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.

    4. For males of reproductive potential: agreement to use of condoms

    5. 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 Cockcroft-Gault formula

    1. Ability to understand and the willingness to sign the IRB approved informed consent document.

    2. Women of childbearing potential must have negative urine or serum pregnancy test

    Exclusion Criteria:
    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. Treatment with iron chelation therapy within 56 days of study start

    4. Significant cardiac disease (NYHA Class IV congestive heart failure, or unstable angina or myocardial infarction within the last 6 months

    5. Harbor IDH2 somatic mutations by NGS or PCR

    6. Pregnant or breast feeding

    7. Any uncontrolled bacterial, fungal, viral or other infection.

    8. 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.

    9. 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 participant can be rescreened and enrolled if nutritionally replete and still meets eligibility criteria.

    10. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford Cancer Institute Palo Alto California United States 94305

    Sponsors and Collaborators

    • Tian Yi Zhang
    • Celgene Corporation

    Investigators

    • Principal Investigator: Tian Yi Zhang, MD, Stanford University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Tian Yi Zhang, Assistant Professor of Medicine (Hematology), Stanford University
    ClinicalTrials.gov Identifier:
    NCT05282459
    Other Study ID Numbers:
    • IRB- 62692
    • HEM0056
    • NCI-2022-02837
    First Posted:
    Mar 16, 2022
    Last Update Posted:
    May 19, 2022
    Last Verified:
    May 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 19, 2022