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NCT05282459

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

Completed Phase 1, PHASE2 Results posted Last updated 17 April 2026
What this trial tests

Phase 1, PHASE2 trial testing Enasidenib mesylat dose escalation in Leukemia in 17 participants. Completed in 3 March 2025.

Timeline
12 January 2022
Primary endpoint
3 December 2024
3 March 2025

Quick facts

Lead sponsorTian Yi Zhang
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment17
Start date12 January 2022
Primary completion3 December 2024
Estimated completion3 March 2025
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Tian Yi Zhang

Who can join

18 and older, any sex, with Leukemia or Leukemia, Myeloid. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clinical Response: Hematological Improvement - Erythroid (HI-E) Primary · 16 weeks

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

GroupValue95% CI
Enasidenib Mesylat 100mg0
Enasidenib Mesylat 200mg0
Related Adverse Events Secondary · 12 months

Toxicity was assessed as the number of related non-serious adverse events and related serious adverse events (SAEs) reported by dose level (Cohort A or Cohort B) for the 12-cycle treatment period plus follow-up.

Related Serious Adverse Events
GroupValue95% CI
Enasidenib Mesylat 100mg0
Enasidenib Mesylat 200mg0
Related Non-Serious Adverse Events
GroupValue95% CI
Enasidenib Mesylat 100mg20
Enasidenib Mesylat 200mg38
Clinical Response: Hematological Improvement - Platelets (HI-P) Secondary · 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.

GroupValue95% CI
Enasidenib Mesylat 100 mg0
Enasidenib Mesylat 200 mg1
Clinical Response: Hematological Improvement - Neutrophils (HI-N) Secondary · 8 weeks

Clinical response for neutrophils was assessed as the number of participants achieving a hematological improvement - neutrophils (HI-N). Response was defined as an absolute increase in neutrophils \> 0.5 × 10\^9/L that was also an increase of ≥ 100%.

GroupValue95% CI
Enasidenib Mesylat 100 mg0
Enasidenib Mesylat 200 mg1
Red Blood Cell (RBC) Transfusion Independence (RBC TI) Secondary · 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.

GroupValue95% CI
Enasidenib Mesylat 100 mg0
Enasidenib Mesylat 200 mg0

Adverse events — posted to ClinicalTrials.gov

Time frame: Informed consent through 90 days after last dose, an average of 9 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Enasidenib Mesylat 100mg
Serious: 3/3 (100%)
Deaths: 1/3
Enasidenib Mesylat 200mg
Serious: 7/14 (50%)
Deaths: 0/14

Serious adverse events (25 terms)

ReactionSystemEnasidenib Mesylat 100mgEnasidenib Mesylat 200mg
AnemiaBlood and lymphatic system disorders
FallInjury, poisoning and procedural complications
Generalized Muscle WeaknessMusculoskeletal and connective tissue disorders
Febrile NeutropeniaBlood and lymphatic system disorders
Chest pain - cardiacCardiac disorders
Blurred visionEye disorders
Duodenal HemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
DiarrheaGastrointestinal disorders
Abdominal painGastrointestinal disorders
Localized EdemaGeneral disorders
FatigueGeneral disorders
Volume overloadGeneral disorders
Ammonium level elevatedHepatobiliary disorders
SepsisInfections and infestations
Lung InfectionInfections and infestations
Urinary tract infectionInfections and infestations
Hip FractureInjury, poisoning and procedural complications
Adult Respiratory Distress SyndromeRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Skin InfectionSkin and subcutaneous tissue disorders
SyncopeNervous system disorders
Intracranial hemorrhageNervous system disorders
Edema CerebralNervous system disorders
VasculitisVascular disorders
Other adverse events (80 terms — click to expand)

ReactionSystemEnasidenib Mesylat 100mgEnasidenib Mesylat 200mg
Bilirubin increasedInvestigations
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
DiarrheaGastrointestinal disorders
VomitingGastrointestinal disorders
PainGeneral disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
AnorexiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
FatigueGeneral disorders
Creatinine increasedInvestigations
Generalized muscle weaknessMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Muscle crampMusculoskeletal and connective tissue disorders
Edema LimbsGeneral disorders
COVID-19Infections and infestations
Urinary tract infectionRenal and urinary disorders
HeadacheNervous system disorders
Acute kidney injuryRenal and urinary disorders
Skin InfectionSkin and subcutaneous tissue disorders
AnemiaBlood and lymphatic system disorders
Elevated Unconjugated BilirubinBlood and lymphatic system disorders
Chest pain - cardiacCardiac disorders
ArthritisMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Rash- UnspecifiedMusculoskeletal and connective tissue disorders
BloatingGastrointestinal disorders
ColitisGastrointestinal disorders
GastritisGastrointestinal disorders
Mucositis oralGastrointestinal disorders
Stomach painGastrointestinal disorders
Abdominal PainGastrointestinal disorders
ChillsGeneral disorders
Duodenal UlcerGeneral disorders
Generalized EdemaGeneral disorders
HemorrhoidsGeneral disorders
Localized EdemaGeneral disorders

Most-reported serious reactions: Anemia, Fall, Generalized Muscle Weakness, Febrile Neutropenia, Chest pain - cardiac, Blurred vision, Duodenal Hemorrhage, Vomiting.

Data from ClinicalTrials.gov NCT05282459 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Altered metabolism in cancer: insights into energy pathways and therapeutic targets.
    Tufail M, Jiang CH, Li N. · · 2024 · cited 265× · PMID 39294640 · DOI 10.1186/s12943-024-02119-3
  2. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
    Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
  3. Next-generation therapy for lower-risk MDS.
    Sébert M. · · 2023 · cited 5× · PMID 38066862 · DOI 10.1182/hematology.2023000520

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing