Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Plain-language summary

This study evaluates the combination of Enasidenib (Enasidenib Mesylate) and Cobimetinib in patients with relapsed or refractory acute myeloid leukemia. Patients aged 18 and older with an IDH2 gene mutation and an accompanying RAS-pathway mutation could take part. The study was conducted in Phase 1 and has been completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

City of Hope Medical Center

Intervention

Cobimetinib, Enasidenib Mesylate

Start date

4/28/2023

Estimated completion

3/19/2026

Countries

United States

Related genes

Locations

• Duarte, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Main Inclusion Criteria

* Patients with histologically confirmed AML, according to WHO criteria, with refractory/relapsed (R/R) disease who are ineligible for therapies known to be effective for treatment of their AML.

  * Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow involvement
  * Patients with acute promyelocytic leukemia (APL) will not be eligible
  * Patients with IDH2 mutations, who were previously treated with enasidenib are allowed
* Have a documented IDH2 gene mutation (≥ 2% allele frequency) and a concomitant detectable RAS-pathway mutation (as determined by local testing), involving NRAS, KRAS, HRAS, BRAF, KIT, RIT1, PTPN11, CBL or NF1 genes.
* Adults aged ≥ 18 years
* ECOG ≤ 2
* WBC ≤25 x 10\^9/L prior to initiation of enasidenib.

Main Exclusion Criteria

* Current or planned use of other investigational agents, antineoplastic, chemotherapy, radiation therapy, biological therapy, immunotherapy or major surgery within 2 weeks or 5 half-lives, whichever is shorter, prior to Day 1 of protocol therapy (exception: hydroxyurea is allowed in cycles 1 and 2 for control of rapidly progressing leukemia or for treatment of enasidenib-related leukocytosis)
* Systemic steroid therapy \> 10 mg/day (≤ 10mg/day prednisone equivalent ok) or any other form of immunosuppressive medication within 28 days, except as required for treatment of differentiation syndrome
* Strong and moderate CYP3A4 inducers/inhibitors (moderate CYP3A4 inhibitors only allowed on Principal Investigator approval) within 14 days or 5 half-lives, whichever is shorter, prior to Day 1 of protocol therapy
* Foods/supplements that are strong or moderate inhibitors or inducers of CYP3A (such as grapefruit, Seville oranges, starfruit and St. John's wort) within 7 days prior to initiation of and during study treatment
* Gastrointestinal disorder such as maladsorption syndrome or any other disorder that may interfere with oral drug absorption
* Clinically significant cardiac morbidities (Class III/IV cardiovascular disability according to the New York Heart Association Classification, arrhythmia not stable on medical management, acute cardiovascular ischemic event within 6 months of enrollment, etc)
* Active CNS disease