Olutasidenib Combined With Co-targeted Therapy in Relapsed or Refractory IDH1-mutated Myeloid Malignancies Harboring Activated Signaling Pathway Mutations
- Conditions
- Targeted TherapyIDH1-Mutated MalignanciesMutations
- Interventions
- Registration Number
- NCT07032727
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
To learn about the safety and tolerability of study drug combinations in patients with relapsed/refractory, IDH1-mutated myeloid malignancies with a co-signaling mutation.
- Detailed Description
Primary Objectives
1. To determine the safety and tolerability of olutasidenib in combination with cladribine + LDAC ± venetoclax (Arm 1), gilteritinib ± venetoclax (Arm 2), and ruxolitinib (Arm 3) for patients with relapsed/refractory IDH1-mutated myeloid malignancies with a co-signaling mutation.
2. To quantify the composite complete remission rate (CRc; CR + CRh + CRi) in patients with relapsed/refractory IDH1-mutated myeloid malignancies with a co-signaling mutation treated with olutasidenib in combination with cladribine + LDAC ± venetoclax (Arm 1), gilteritinib ± venetoclax (Arm 2), and ruxolitinib (Arm3).
Secondary Objectives
1. To determine overall survival (OS), event free survival (EFS), and duration of response (DOR) with olutasidenib in combination with a co-targeting chemotherapeutic agent.
2. To determine the overall response rate (ORR; CR + CRh + CRi + MLFS + PR) of olutasidenib in combination with a co-targeting chemotherapeutic agent.
3. To evaluate occurrence of measurable residual disease (MRD) negative status by multiparameter flow cytometry and molecular evaluation by polymerase chain reaction (PCR) and next generation sequencing (NGS)-based assays (e.g. IDH1 and FLT3 if applicable).
4. To characterize the pharmacokinetic (PK) profiles of olutasidenib and venetoclax in plasma samples.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 68
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 3A Safety Lead-In/Expansion: Olutasidenib Treatment with Olutasidenib + Ruxolitinib Arm 3A Safety Lead-In/Expansion: Ruxolitinib Treatment with Olutasidenib + Ruxolitinib Arm 1A Safety Lead-In/Expansion: Olutasidenib Treatment with Olutasidenib + Cladribine + Cytarabine Arm 1A Safety Lead-In/Expansion: Cladribine (CLAD) Treatment with Olutasidenib + Cladribine + Cytarabine Arm 1A Safety Lead-In/Expansion: Cytarabine Treatment with Olutasidenib + Cladribine + Cytarabine Arm 1B Expansion Olutasidenib Treatment with Olutasidenib + Cladribine + Cytarabine + Venetoclax Arm 1B Expansion Cladribine (CLAD) Treatment with Olutasidenib + Cladribine + Cytarabine + Venetoclax Arm 1B Expansion Venetoclax Treatment with Olutasidenib + Cladribine + Cytarabine + Venetoclax Arm 1B Expansion Cytarabine Treatment with Olutasidenib + Cladribine + Cytarabine + Venetoclax Arm 2A Safety Lead-In/Expansion Olutasidenib Treatment with Olutasidenib + Gilteritnib Arm 2A Safety Lead-In/Expansion Gilteritinib Treatment with Olutasidenib + Gilteritnib Arm 2B Expansion Olutasidenib Treatment with Olutasidenib + Gilteritnib + Venetoclax Arm 2B Expansion Venetoclax Treatment with Olutasidenib + Gilteritnib + Venetoclax Arm 2B Expansion Gilteritinib Treatment with Olutasidenib + Gilteritnib + Venetoclax
- Primary Outcome Measures
Name Time Method Safety and adverse events (AEs) Through study completion; an average of 1 year Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center🇺🇸Houston, Texas, United StatesCourtney DiNardo, MDPrincipal Investigator