A Phase 1 Study of Menin-KMT2A Inhibitor Ziftomenib (KO-539) in Combination With Cereblon E3 Ligase Modulator Mezigdomide (CC-92480) in Adolescents and Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Massachusetts General Hospital
Summary
The purpose of this study is to evaluate the safety and tolerability of mezigdomide in combination with ziftomenib in adolescent and adult participants with either KMT2A-rearranged (KMT2A-r) or NPM1-mutant relapsed or refractory acute myeloid leukemia (AML).
Description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied. The U.S. Food and Drug Administration (FDA) has not approved ziftomenib and mezigdomide as a treatment for any disease. Duration of treatment will depend on individual response, evidence of disease progression, and tolerance. The total treatment period will be 12 cycles. If you have completed treatment, you will be followed of up to 12 mon…
Eligibility
- Age range
- 12+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Age ≥16 years during dose escalation portion of study, patients must weigh ≥40 kg. * Age \>12 years during dose expansion portion of study, patients must weight ≥40 kg. * Diagnosis of AML per the WHO Classification of Hematolymphoid Tumors (5th Edition) with documented KMT2A rearrangement or NPM1 cytoplasmic-type (NPM1c) mutation. KMT2A-rearrangements must be confirmed by FISH or RNA-based fusion calling by a CLIA-certified laboratory. This study will only enroll KMT2A gene rearrangements in which there is a translocation between the N-terminal portion of KMT2A and a fus…
Interventions
- DrugZiftomenib
Capsule taken orally once daily on days 1-28 of each 28-day cycle.
- DrugMezigdomide
Capsule taken orally once daily on days 1-21 or possibly days 1-14 of each 28-day cycle.
Locations (2)
- Massachusetts General HospitalBoston, Massachusetts
- Dana-Farber Cancer InstituteBoston, Massachusetts