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A Study of HMPL-306 in Advanced Hematological Malignancies With mIDH

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: NCT04764474
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : April 15, 2021
Sponsor:
Information provided by (Responsible Party):
Hutchison Medipharma Limited

Tracking Information
First Submitted Date  ICMJE January 19, 2021
First Posted Date  ICMJE February 21, 2021
Last Update Posted Date April 15, 2021
Actual Study Start Date  ICMJE February 28, 2021
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2021)
  • Part 1: Number of Subjects with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days after first dose of study drug ]
    DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
  • Part 1 and Part 2: Frequency and severity of AEs [ Time Frame: From the first dose of the study drug to 37 days after the last dose of study drug ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2021)
  • Number of Subjects with Complete Response (CR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
  • Number of Subjects with Complete Response with Incomplete Marrow Recovery (CRi [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
  • Number of Subjects with Complete Response with Negative Minimal Residual Disease (CRMRD-) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
  • Number of Subjects with Partial Response (PR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
  • Number of Subjects with Stable Disease (SD) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
    Subjects who have not achieved a CR, CRi, CRMRD-, morphologically leukemia-free state (MLFS), or PR but have no evidence of progression of disease in >8 weeks.
  • Objective Response Rate (ORR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
    ORR is defined as the proportion of subjects achieving PR and better response during the study [CR + CRi + marrow CR/MLFS + PR].
  • Clinical Benefit Rate (CBR) [ Time Frame: From 1st dose of study drug to the time of progressive disease, assessed up to 36 months ]
    CBR is defined as the proportion of subjects achieving objective response or SD.
  • Overall survival (OS) [ Time Frame: From first dose of study drug to end of study or death, assessed up to 36 months ]
    OS is defined as the time from the start of the study drug until death from any cause.
  • Proportion of non-blood transfusion dependent subjects [ Time Frame: From the first dose of study drug to last dose of study drug, assessed up to 36 months ]
    It is defined as the proportion of subjects who do not need blood transfusion for any sequential period ≥8 weeks during the study treatment period.
  • Maximum serum drug concentration [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]
    Blood samples will be obtained from all patients for determination of the maximum serum concentration of HMPL-306
  • Time to maximum concentration [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]
    Blood samples will be obtained from all patients for determination time to maximum concentration of HMPL-306
  • Area under the concentration-time curve (AUC) [ Time Frame: PK weeks at screening through safety follow-up, assessed up to 36 months ]
    Blood samples will be obtained from all patients for determination of the AUC of HMPL-306
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 Advanced Hematological Malignancies With mIDH
Official Title  ICMJE A Phase 1, Open-Label, Multicenter Study of HMPL-306 in Advanced Hematological Malignancies With Isocitrate Dehydrogenase (IDH) Mutations
Brief Summary An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 in subjects with advanced relapsed, refractory, or resistant hematological malignancies that harbor IDH mutations.
Detailed Description

HMPL-306 is a dual IDH1/2 inhibitor

This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of HMPL-306 administered orally in treatment of subjects with advanced relapsed, refractory, or resistant hematological malignancies that harbor IDH mutations (or co-mutations).

The study consists of 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). The dose-escalation part will determine the MTD/R2PD. The dose-expansion part will administer the MTD/RP2D to subjects with mIDH-positive hematological malignancies including, but not limited to, AML, MDS/MPN, AITL.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Isocitrate Dehydrogenase Gene Mutation
Intervention  ICMJE Drug: HMPL-306
Administered orally QD in a 28-day continuous dosing treatment cycle
Study Arms  ICMJE
  • Experimental: Part 1 Dose Escalation Cohorts
    Patients from each cohort will be administered HMPL-306 orally QD
    Intervention: Drug: HMPL-306
  • Experimental: Part 2 Dose Expansion Cohorts
    Patients from each cohort will be administered HMPL-306 orally QD at the recommended phase 2 dose
    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 17, 2021)
75
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 31, 2023
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

Subjects may be enrolled in this study only if they satisfy all the following criteria (NOTE: This is not an exhaustive list):

  • Subjects aged ≥18 years.
  • ECOG performance status ≤ 2
  • Subjects with advanced relapsed, refractory, or resistant hematological malignancies, as defined below:
  • Subjects with documented IDH mutation per local or institutional next generation sequence (NGS).
  • Subjects must be refractory to or intolerant of established therapies

Key Exclusion Criteria:

Subjects are not eligible for enrollment into this study if they meet any of the following criteria (NOTE: This is not an exhaustive list):

  • Subjects who received an investigational agent <14 days prior to their first day of study drug administration
  • Subjects who are pregnant or breastfeeding
  • Subjects with an active severe infection, some treated infections and with an expected or with an unexplained fever >38.3°C during screening visits or on their first day of study drug administration.
  • Subjects with some current or prior heart conditions
  • Subjects taking medications that are known to prolong the QT interval may not be eligible
  • Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation
  • Some subjects with some current or prior gastrointestinal or liver diseases
  • Subjects with inadequate organ function as defined by the protocol
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: Vijay Jayaprakash, MBBS, PHD 973-900-6617 vijayj@hmplglobal.com
Contact: Alisha Khullar, MS 973 287 3081 alishak@hmplglobal.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04764474
Other Study ID Numbers  ICMJE 2020-306-GLOB1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
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: Vijay Jayaprakash, MBBS, PHD Hutchison Medipharma Limited
PRS Account Hutchison Medipharma Limited
Verification Date December 2020

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