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

Primary Purpose

Acute Myeloid Leukemia

Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HMPL-306
Sponsored by
Hutchison Medipharma Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring HMPL-306, IDH1 Mutation, IDH2 Mutation, Acute myeloid leukemia, Myelodysplastic symdrome, Chronic myelomonocytic leukemia, Myeloid Leukemia/Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Peking University People's HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HMPL-306

Arm Description

HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.

Outcomes

Primary Outcome Measures

Safety and tolerability: Incidence of adverse events
Incidence of adverse events.
Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)
Measured by adverse event profile.

Secondary Outcome Measures

Cmax (Cycle 1 Day 1) of HMPL-306
Cmax: maximum observed drug concentration in measured matrix after single dose administration.
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.
AUC(0-tlast) (Cycle 1 Day 1) of HMPL-306
AUC from time zero to the last data point.
Objective Response Rate (ORR)
proportion of patients with confirmed complete response (CR) and partial response (PR).
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.
Progression-free survival (PFS)
PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression.
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.

Full Information

First Posted
February 13, 2020
Last Updated
June 12, 2020
Sponsor
Hutchison Medipharma Limited
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1. Study Identification

Unique Protocol Identification Number
NCT04272957
Brief Title
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

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Unknown status
Study Start Date
May 14, 2020 (Actual)
Primary Completion Date
June 30, 2021 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hutchison Medipharma Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
HMPL-306, IDH1 Mutation, IDH2 Mutation, Acute myeloid leukemia, Myelodysplastic symdrome, Chronic myelomonocytic leukemia, Myeloid Leukemia/Neoplasms

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HMPL-306
Arm Type
Experimental
Arm Description
HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
HMPL-306
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety and tolerability: Incidence of adverse events
Description
Incidence of adverse events.
Time Frame
Baseline up to the last patient has completed the 24 weeks of treatment
Title
Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)
Description
Measured by adverse event profile.
Time Frame
Baseline up to the last patient has completed the 24 weeks of treatment
Secondary Outcome Measure Information:
Title
Cmax (Cycle 1 Day 1) of HMPL-306
Description
Cmax: maximum observed drug concentration in measured matrix after single dose administration.
Time Frame
Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
Title
AUC(0-24) (Cycle 1 Day 1) of HMPL-306
Description
AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose.
Time Frame
Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
Title
AUC(0-tlast) (Cycle 1 Day 1) of HMPL-306
Description
AUC from time zero to the last data point.
Time Frame
Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
Title
Objective Response Rate (ORR)
Description
proportion of patients with confirmed complete response (CR) and partial response (PR).
Time Frame
Baseline up to the last patient has completed the 24 weeks of treatment
Title
Duration of response (DOR)
Description
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.
Time Frame
Baseline up to the last patient has completed the 24 weeks of treatment
Title
Progression-free survival (PFS)
Description
PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression.
Time Frame
Baseline up to the last patient has completed the 24 weeks of treatment
Title
Overall survival (OS)
Description
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.
Time Frame
Baseline up to the last patient has completed the 24 weeks of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xianlin Duan
Phone
02120678852
Email
xianlind@hmplglobal.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lang Zhang
Phone
02120673224
Email
langz@hmplglobal.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weiss Yang
Organizational Affiliation
Hutchison MediPharma Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaojun Huang, Professor
Email
huangxiaojun@bjmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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