Ziftomenib + Mezigdomide in Adolesc. and Adults w/ R/R AML
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12+
SponsorMassachusetts General Hospital
About this trial
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).
Eligibility criteria
Qualifiers
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 fusion partner, and will not include KMT2A partial tandem duplications (PTDs) or other structural alterations of KMT2A. NPM1c mutations must be confirmed by DNA sequencing in a CLIA-certified laboratory. Patients with myeloid sarcoma are eligible only if concurrent bone marrow involvement is present. Patients must have at least 5% bone marrow disease by morphology at the time of study entry.
Patients with NPM1 mutated AML must either be FLT3 ITD wild type or have an ITD allelic ratio of <0.05 (i.e. not eligible for a targeted FLT3 tyrosine kinase inhibitor).
Disqualifiers
AML diagnosis without KMT2A-rearrangement or NPM1-mutation. KMT2A-PTD patients and patients with KMT2A alterations other than translocations are excluded.
Active central nervous system (CNS) involvement by AML (i.e., CNS-2 or CNS-3 disease). Previously treated CNS disease or those receiving prophylactic intrathecal chemotherapy per institutional standard is allowed.
Myeloid sarcoma or extramedullary disease without bone marrow disease.
Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1 by the NCI-CTCAE version 5.0) with the exception of alopecia.
Trial design
Treatments tested in this trial
- Ziftomenib
- Mezigdomide
Treatment groups
24 Participants
are divided into 1 treatment groupSponsors and collaborators
Massachusetts General Hospital
Lead sponsor
Kura Oncology, Inc.
Collaborator
Bristol-Myers Squibb
Collaborator
Source ClinicalTrials.gov