A Study of HMPL-306 in Patients With IDH1 and/or IDH2 Mutation of Relapsed/Refractory Myeloid Leukemia/Neoplasms

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: HMPL-306

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 Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking University People's Hospital
      • Contact: Xiaojun Huang, Professor; Email: huangxiaojun@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HMPL-306; HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.	Drug: HMPL-306; HMPL-306 administered continuously as a single agent starting at 25 mg orally every day in a 28-day cycle and dose escalation is planned up to 200mg. Subjects may continue treatment with HMPL-306 until disease progression, development of other unacceptable toxicity or hematopoietic stem cell transplant.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability: Incidence of adverse events	Incidence of adverse events.	Baseline up to the last patient has completed the 24 weeks of treatment
Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)	Measured by adverse event profile.	Baseline up to the last patient has completed the 24 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (Cycle 1 Day 1) of HMPL-306	Cmax: maximum observed drug concentration in measured matrix after single dose administration.	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	AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose.	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	AUC from time zero to the last data point.	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)	proportion of patients with confirmed complete response (CR) and partial response (PR).	Baseline up to the last patient has completed the 24 weeks of treatment
Duration of response (DOR)	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.	Baseline up to the last patient has completed the 24 weeks of treatment
Progression-free survival (PFS)	PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression.	Baseline up to the last patient has completed the 24 weeks of treatment
Overall survival (OS)	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.	Baseline up to the last patient has completed the 24 weeks of treatment

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Study Director: Weiss Yang, Hutchison MediPharma Ltd

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 14, 2020
• Primary Completion (ANTICIPATED): June 30, 2021
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: February 13, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (ACTUAL): February 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 16, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Acute myeloid leukemia; Chronic myelomonocytic leukemia; HMPL-306; IDH1 Mutation; IDH2 Mutation; Myelodysplastic symdrome; Myeloid Leukemia/Neoplasms
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 2018-306-00CH1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No