Ziftomenib + Mezigdomide in Adolesc. and Adults w/ R/R AML
Trial statusRecruiting
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
This trial does not accept healthy volunteersQualifiers
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 6.0) with the exception of alopecia.
Trial design
Design model
Single group
Treatments tested in this trial
Ziftomenib
DrugCapsule taken orally once daily on days 1-28 of each 28-day cycle.
Mezigdomide
DrugCapsule taken orally once daily on days 1-21 or possibly days 1-14 of each 28-day cycle.
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: Ziftomenib and MezigdomideExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
To characterize the safety and tolerability of mezigdomide in combination with ziftomenib, all reported toxicities will be summarized by toxicity type and maximum grade and will be reported as numbers and percentages. All participants who receive at least one dose of study treatments will be evaluable for toxicity.
Time frame
From the start of treatment until participant withdrawal, death, or removal from study, whichever comes first, assessed up to 2 years after initial dose of study treatment.2
Recommended phase 2 dose (RP2D) of mezigdomide in combination with ziftomenib.
The RP2D of mezigdomide in combination with ziftomenib will be determined in the dose escalation phase via a traditional 3+3 dose escalation design.
Time frame
From start of treatment to end of 12 cycles (each cycle is 28 days).Secondary outcomes
1
Complete remission/complete remission with partial hematologic recovery (CR/CRh) and overall response rate (ORR)
CR/CRh rate and overall response rate will be summarized using point estimates and exact binomial 90% confidence intervals in patients treated with RP2D.
Time frame
From start of treatment to end of 12 cycles (each cycle is 28 days) or until participant withdrawal, death, or removal from study, whichever comes first.2
2-year overall and relapse-free survival rates
Two-year overall survival and relapse-free survival will be estimated using the Kaplan-Meier method with 90% confidence intervals.
Time frame
From the start of treatment until participant withdrawal, death, or removal from study, whichever comes first, assessed up to 2 years after initial dose of study treatment.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Massachusetts General Hospital
Lead sponsor
Kura Oncology, Inc.
Collaborator
Bristol-Myers Squibb
Collaborator
Source ClinicalTrials.gov