A Study of HMPL-306 in Patients With IDH1 and/or IDH2 Mutation of Relapsed/Refractory Myeloid Leukemia/Neoplasms
- Registration Number
- NCT04272957
- Lead Sponsor
- Hutchison Medipharma Limited
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 75
- ≥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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HMPL-306 HMPL-306 HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.
- Primary Outcome Measures
Name Time Method Safety and tolerability: Incidence of adverse events 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) Baseline up to the last patient has completed the 24 weeks of treatment Measured by adverse event profile.
- Secondary Outcome Measures
Name Time Method 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 Cmax: maximum observed drug concentration in measured matrix after single dose administration.
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: area under the concentration vs. time curve from zero to infinity after single (first) dose.
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 AUC from time zero to the last data point.
Objective Response Rate (ORR) Baseline up to the last patient has completed the 24 weeks of treatment proportion of patients with confirmed complete response (CR) and partial response (PR).
Duration of response (DOR) Baseline up to the last patient has completed the 24 weeks of treatment DOR is defined as the time from the date of first observed tumor response (Complete response (CR) or Partial response (PR)) until first subsequent disease progression or until death (if death occurs before progression is documented) due to any cause.
Progression-free survival (PFS) Baseline up to the last patient has completed the 24 weeks of treatment PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression.
Overall survival (OS) Baseline up to the last patient has completed the 24 weeks of treatment OS is defined as the time from enrollment (i.e., date of treatment assignment) until death from any cause or until the last date the patient is known to be alive.
Trial Locations
- Locations (1)
Peking University People's Hospital
🇨🇳Beijing, Beijing, China