Combining enasidenib and cobimetinib for treating relapsed or refractory acute myeloid leukemia
Phase 1b Study of IDH Inhibition With Enasidenib and MEK Inhibition With Cobimetinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Have Co-Occurring IDH2 and RAS Signaling Gene Mutations
This study is testing if combining two drugs, enasidenib and cobimetinib, can help people with relapsed or refractory acute myeloid leukemia feel better and improve their chances of recovery.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | City of Hope Medical Center Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, radiation, prednisone, cobimetinib |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT05441514 on ClinicalTrials.gov |
What this trial studies
This phase Ib trial evaluates the safety and effectiveness of enasidenib combined with cobimetinib in patients with relapsed or refractory acute myeloid leukemia (AML). The study aims to determine the maximum tolerated dose and assess clinical activity through various response rates and survival metrics. Enasidenib works by inhibiting enzymes necessary for cancer cell growth, while cobimetinib targets mutated BRAF proteins that promote cancer cell proliferation. The trial will also explore changes in cellular differentiation and gene expression in response to the treatment.
Who should consider this trial
Good fit: Ideal candidates include adults with relapsed or refractory acute myeloid leukemia who have specific IDH2 and RAS-pathway mutations.
Not a fit: Patients with acute promyelocytic leukemia or those currently receiving other investigational or antineoplastic therapies may not benefit from this study.
Why it matters
Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with difficult-to-treat forms of acute myeloid leukemia.
How similar studies have performed: While the combination of these specific agents is novel, similar approaches targeting genetic mutations in cancer have shown promise in other studies.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (Recruiting)
Study contacts
- Principal investigator: Brian Ball — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.