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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04272957
• Other study ID #: 2018-306-00CH1
• Status: Recruiting
• Phase: Phase 1
• Start date: May 14, 2020
• Est. completion date: December 30, 2022

Study information

• Verified date: June 2020
• Source: Hutchison Medipharma Limited
• Contact: Xianlin Duan
• Phone: 02120678852
• Email: xianlind[@]hmplglobal.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: December 30, 2022
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasms

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.

Locations

Country	Name	City	State
China	Peking University People's Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability: Incidence of adverse events	Incidence of adverse events.	Baseline up to the last patient has completed the 24 weeks of treatment
Primary	Maximum tolerated dosage (MTD) and/or recommended phase 2 dosage (RP2D)	Measured by adverse event profile.	Baseline up to the last patient has completed the 24 weeks of treatment
Secondary	Cmax (Cycle 1 Day 1) of HMPL-306	Cmax: maximum observed drug concentration in measured matrix after single dose administration.	Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
Secondary	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.	Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
Secondary	AUC(0-tlast) (Cycle 1 Day 1) of HMPL-306	AUC from time zero to the last data point.	Pre-dose, 10 minutes, 1, 1.5, 2, 3, 5, 8, 11, 24, 48, 72, 120 and 168 hours after start
Secondary	Objective Response Rate (ORR)	proportion of patients with confirmed complete response (CR) and partial response (PR).	Baseline up to the last patient has completed the 24 weeks of treatment
Secondary	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.	Baseline up to the last patient has completed the 24 weeks of treatment
Secondary	Progression-free survival (PFS)	PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression.	Baseline up to the last patient has completed the 24 weeks of treatment
Secondary	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.	Baseline up to the last patient has completed the 24 weeks of treatment