Status:
ACTIVE_NOT_RECRUITING
Enasidenib in Combination With Cobimetinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia
Lead Sponsor:
City of Hope Medical Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Recurrent Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This phase Ib trial tests the safety, side effects, and best dose of a enasidenib in combination with cobimetinib in treating patients with acute myeloid leukemia that has come back (relapsed) or does...
Detailed Description
PRIMARY OBJECTIVES: I. Assess the safety and tolerability of cobimetinib in combination with enasidenib. II. Determine the maximum tolerated dose(s) (MTD) and recommended phase 2 dose (RP2D). SECON...
Eligibility Criteria
Inclusion
- 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
Exclusion
Key Trial Info
Start Date :
November 3 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 3 2027
Estimated Enrollment :
3 Patients enrolled
Trial Details
Trial ID
NCT05441514
Start Date
November 3 2022
End Date
May 3 2027
Last Update
September 16 2025
Active Locations (1)
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1
City of Hope Medical Center
Duarte, California, United States, 91010