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

• ClinicalTrials.gov Identifier: NCT04272957
• Recruitment Status: Recruiting
• First Posted: February 17, 2020
• Last Update Posted: June 16, 2020
• Sponsor: Hutchison Medipharma Limited
• Information provided by (Responsible Party): Hutchison Medipharma Limited

Tracking Information

• First Submitted Date: February 13, 2020
• First Posted Date: February 17, 2020
• Last Update Posted Date: June 16, 2020
• Actual Study Start Date: May 14, 2020
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia

Intervention

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

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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 13, 2020): 75
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2022
• Estimated Primary Completion Date: June 30, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Xianlin Duan; 02120678852; xianlind@hmplglobal.com

Contact: Lang Zhang; 02120673224; langz@hmplglobal.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04272957
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Hutchison Medipharma Limited
• Study Sponsor: Hutchison Medipharma Limited
• Collaborators: Not Provided

Investigators

• Study Director: Weiss Yang; Hutchison MediPharma Ltd

• PRS Account: Hutchison Medipharma Limited
• Verification Date: June 2020