Clinical trial NCT04272957: A Study of HMPL-306 in Patients With IDH1 and/or IDH2 Mutation of Relapsed/Refractory Myeloid Leukemia/Neoplasms
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: HMPL-306
IDH1 Mutation
IDH2 Mutation
Acute myeloid leukemia
Myelodysplastic symdrome
Chronic myelomonocytic leukemia
Myeloid Leukemia/Neoplasms
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability: Incidence of adverse events
timeFrame: Baseline up to the last patient has completed the 24 weeks of treatment
measure: Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)
timeFrame: Baseline up to the last patient has completed the 24 weeks of treatment
Secondary outcomes:
measure: Cmax (Cycle 1 Day 1) of HMPL-306
timeFrame: Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
measure: AUC(0-24) (Cycle 1 Day 1) of HMPL-306
timeFrame: Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
measure: AUC(0-tlast) (Cycle 1 Day 1) of HMPL-306
timeFrame: Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to the last patient has completed the 24 weeks of treatment
measure: Duration of response (DOR)
timeFrame: Baseline up to the last patient has completed the 24 weeks of treatment
measure: Progression-free survival (PFS)
timeFrame: Baseline up to the last patient has completed the 24 weeks of treatment
measure: Overall survival (OS)
timeFrame: Baseline up to the last patient has completed the 24 weeks of treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Hutchison MediPharma Ltd
name: Weiss Yang
role: STUDY_DIRECTOR
References: