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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04272957
Recruitment Status : Recruiting
First Posted : February 17, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE February 13, 2020
First Posted Date  ICMJE February 17, 2020
Last Update Posted Date June 16, 2020
Actual Study Start Date  ICMJE May 14, 2020
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 18, 2020)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 13, 2020)
  • Safety and tolerability [ Time Frame: Baseline up to the last patient has completed the 24 weeks of treatment ]
    Incidence of adverse events.Toxicity will be graded according to the NCI-CTCAC version 4.0.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2020)
  • Cmax (Cycle 1 Day 1) of HMPL-306 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of HMPL-306 in Patients With IDH1 and/or IDH2 Mutation of Relapsed/Refractory Myeloid Leukemia/Neoplasms
Official Title  ICMJE 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
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: HMPL-306
HMPL-306 administered continuously as a single agent orally every day in a 28-day cycle.
Intervention: Drug: HMPL-306
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 13, 2020)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xianlin Duan 02120678852 xianlind@hmplglobal.com
Contact: Lang Zhang 02120673224 langz@hmplglobal.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04272957
Other Study ID Numbers  ICMJE 2018-306-00CH1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hutchison Medipharma Limited
Study Sponsor  ICMJE Hutchison Medipharma Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Weiss Yang Hutchison MediPharma Ltd
PRS Account Hutchison Medipharma Limited
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP