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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

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: HMPL-306 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 14, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 30, 2022


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.




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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).

  5. 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.

  6. 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.

  7. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04272957


Contacts
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Contact: Xianlin Duan 02120678852 xianlind@hmplglobal.com
Contact: Lang Zhang 02120673224 langz@hmplglobal.com

Locations
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China, Beijing
Peking University People's Hospital Recruiting
Beijing, Beijing, China
Contact: Xiaojun Huang, Professor       huangxiaojun@bjmu.edu.cn   
Sponsors and Collaborators
Hutchison Medipharma Limited
Investigators
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Study Director: Weiss Yang Hutchison MediPharma Ltd
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Responsible Party: Hutchison Medipharma Limited
ClinicalTrials.gov Identifier: NCT04272957    
Other Study ID Numbers: 2018-306-00CH1
First Posted: February 17, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hutchison Medipharma Limited:
HMPL-306
IDH1 Mutation
IDH2 Mutation
Acute myeloid leukemia
Myelodysplastic symdrome
Chronic myelomonocytic leukemia
Myeloid Leukemia/Neoplasms
Additional relevant MeSH terms:
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Leukemia
Neoplasms
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type