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NCT03724084

Pinometostat With Standard Chemotherapy in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia and MLL Gene Rearrangement

Terminated Phase 1, PHASE2 Results posted Last updated 18 June 2025
What this trial tests

Phase 1, PHASE2 trial testing Cytarabine in Acute Myeloid Leukemia in 6 participants. Terminated before completion.

Timeline
10 April 2019
Primary endpoint
14 November 2022
14 November 2022

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment6
Start date10 April 2019
Primary completion14 November 2022
Estimated completion14 November 2022
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

14 and older, any sex, with Acute Myeloid Leukemia. 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.

Dose Limiting Toxicity (Phase Ib) Primary · Up to 35 days

Dose escalation for phase 1b will be in the usual 3+3 fashion

GroupValue95% CI
Cohort I (Higher and Lower Dose Pinometostat)0
Cohort II (Higher Dose Pinometostat)0
Complete Response (CR) or Complete Response With Incomplete Count Recovery (CRi) Rate Primary · Up to 3 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

GroupValue95% CI
Cohort I (Higher and Lower Dose Pinometostat)3
Cohort II (Higher Dose Pinometostat)2
Number of Participants With Incidence of Adverse Events Secondary · For up to 3 years

Will be graded and reported according to Common Terminology Criteria for Adverse Events version 5. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Any grade
GroupValue95% CI
Cohort I (Higher and Lower Dose Pinometostat)3
Cohort II (Higher Dose Pinometostat)3
Grade 4
GroupValue95% CI
Cohort I (Higher and Lower Dose Pinometostat)3
Cohort II (Higher Dose Pinometostat)2
Progression Free Survival Secondary · From the start of study treatment until progression or death, whichever occurs earliest, assessed up to 3 years

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

GroupValue95% CI
Cohort I (Higher and Lowers Dose Pinometostat)10095 – 133
Cohort II (Higher Dose Pinometostat)400400 – 400
Overall Survival Secondary · Up to 3 years

Estimated using the Kaplan-Meier method.

GroupValue95% CI
Cohort I (Higher and Lowers Dose Pinometostat)326181 – 450
Cohort II (Higher Dose Pinometostat)298168 – 428

Adverse events — posted to ClinicalTrials.gov

Time frame: The Adverse event information was collected for study patients from baseline through study completion utilizing the CTCAE version 5.0 to determine the severity of the reaction for adverse event reporting from baseline to after study completion, up to 2 years, All-Cause Mortality monitored/assessed up to 3 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort I (Higher and Lower Dose Pinometostat)
Serious: 3/3 (100%)
Deaths: 2/3
Cohort II (Higher Dose Pinometostat)
Serious: 1/3 (33%)
Deaths: 1/3

Serious adverse events (1 terms)

ReactionSystemCohort I (Higher and Lower…Cohort II (Higher Dose Pin…
White blood cell decreasedInvestigations
Other adverse events (21 terms — click to expand)

ReactionSystemCohort I (Higher and Lower…Cohort II (Higher Dose Pin…
AnemiaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell decreasedInvestigations
DiarrheaGastrointestinal disorders
HeadacheNervous system disorders
AnorexiaMetabolism and nutrition disorders
BruisingInjury, poisoning and procedural complications
Edema LimbsGeneral disorders
FatigueGeneral disorders
Lung InfectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
INR increasedInvestigations
HypocalcemiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HyperphosphatemiaMetabolism and nutrition disorders
coughRespiratory, thoracic and mediastinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders

Most-reported serious reactions: White blood cell decreased.

Data from ClinicalTrials.gov NCT03724084 adverse events section.

Sponsor's own description

This phase Ib/II trial studies the side effects and best dose of pinometostat and how well it works with standard chemotherapy in treating patients with newly diagnosed acute myeloid leukemia and a type of genetic mutation called MLL gene rearrangement. Pinometostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in standard chemotherapy, such as daunorubicin hydrochloride and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pinometostat with standard chemotherapy may work better at treating acute myeloid leukemia.

Publications & conference data

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

  1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
    Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
  2. Tumor biomarkers for diagnosis, prognosis and targeted therapy.
    Zhou Y, Tao L, Qiu J, Xu J, et al · · 2024 · cited 379× · PMID 38763973 · DOI 10.1038/s41392-024-01823-2
  3. Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease.
    Bhat KP, Ümit Kaniskan H, Jin J, Gozani O. · · 2021 · cited 181× · PMID 33469207 · DOI 10.1038/s41573-020-00108-x
  4. Epigenetics-targeted drugs: current paradigms and future challenges.
    Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
  5. Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis.
    Yamashita M, Dellorusso PV, Olson OC, Passegué E. · · 2020 · cited 128× · PMID 32415283 · DOI 10.1038/s41568-020-0260-3
  6. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
    Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x
  7. Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches.
    Winer ES, Stone RM. · · 2019 · cited 92× · PMID 31321011 · DOI 10.1177/2040620719860645
  8. Methylation across the central dogma in health and diseases: new therapeutic strategies.
    Liu R, Zhao E, Yu H, Yuan C, et al · · 2023 · cited 79× · PMID 37620312 · DOI 10.1038/s41392-023-01528-y

Verify or expand the search:

Other trials of Cytarabine

Trials testing the same drug.

Other recruiting trials for Acute Myeloid Leukemia

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03724084.

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