A Phase I, Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics and Efficacy of HMPL-306 in Patients of Relapsed/Refractory Myeloid Leukemia/Neoplasms With IDH1 and/or IDH2 Mutation
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- Safety and tolerability: Incidence of adverse events
Study Overview
Brief Summary
Phase I, multicenter study to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in Patients of Relapsed/Refractory Myeloid Leukemia/Neoplasms with IDH1 and/or IDH2 Mutation.
Detailed Description
The purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in Patients of Relapsed/Refractory Myeloid Leukemia/Neoplasms with IDH1 and/or IDH2 Mutation. The first stage of the study is a dose escalation phase where cohorts of patients will receive ascending oral doses of HMPL-306 to determine maximum tolerated dose (MTD) and/or the recommended Phase II dose. The second stage of the study is a dose expansion phase where three cohorts of patients will receive HMPL-306 to further evaluate the safety, tolerability, and clinical activity of the recommended Phase II dose.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •≥18 years of age;
- •Signed Informed Consent Form;
- •Relapsed/refractory Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia(CMML) and others myeloid neoplasm;
- •IDH1 and/or IDH2 mutated disease status as assessed by local laboratory;
- •Cooperative Oncology Group (ECOG) performance status of 0-2;
- •Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study.
Exclusion Criteria
- •Previously treated with any prior IDH1 inhibitor, IDH2 inhibitor, or IDH1/IDH2 double-targeted therapy and had disease progression during treatment;
- •with known involvement or clinical symptoms of central nervous system (CNS);
- •Patients who have undergone HSCT within 60 days;
- •Without adequate liver or kidney function;
- •With known infection with active hepatitis B or C;
- •With known infection with human immunodeficiency virus (HIV);
- •History of clinically significant or active cardiac disease;
- •Active clinically significant infection;
- •Taking known strong cytochrome P450 (CYP) 2C8 inducers or inhibitors;
- •Pregnancy or breast-feeding.
Arms & Interventions
HMPL-306
HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.
Intervention: HMPL-306 (Drug)
Outcomes
Primary Outcomes
Safety and tolerability: Incidence of adverse events
Time Frame: Baseline up to the last patient has completed the 24 weeks of treatment
Incidence of adverse events.
Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)
Time Frame: Baseline up to the last patient has completed the 24 weeks of treatment
Measured by adverse event profile.
Secondary Outcomes
- Cmax (Cycle 1 Day 1) of HMPL-306(Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start)
- AUC(0-24) (Cycle 1 Day 1) of HMPL-306(Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start)
- AUC(0-tlast) (Cycle 1 Day 1) of HMPL-306(Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start)
- Objective Response Rate (ORR)(Baseline up to the last patient has completed the 24 weeks of treatment)
- Duration of response (DOR)(Baseline up to the last patient has completed the 24 weeks of treatment)
- Progression-free survival (PFS)(Baseline up to the last patient has completed the 24 weeks of treatment)
- Overall survival (OS)(Baseline up to the last patient has completed the 24 weeks of treatment)