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HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Primary Purpose

B-Cell Non-Hodgkin's Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HMPL-760
Sponsored by
Hutchison Medipharma Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-Cell Non-Hodgkin's Lymphoma focused on measuring B-Cell Non-Hodgkin's Lymphoma, Bruton's tyrosine kinase inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed Informed Consent Form (ICF)
  2. Age ≥18 years
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2
  4. Relapsed/refractory patients with histologically confirmed lymphoma or cytologically confirmed CLL (flow cytometry)
  5. At least one bidimensionally measurable lesion by CT with the exception of CLL, i.e., nodal lesions > 1.5 cm in maximal diameter or extranodal lesions > 1.0 cm;
  6. Expected survival longer than 24 weeks

Exclusion Criteria:

Patients who met any of the following criteria are excluded from the study:

  1. Lymphoma patients with central nervous system (CNS) or leptomeningeal invasion
  2. Inadequate organ function of liver and kidney
  3. Carcinoma in situ of the breast History of liver disease, including cirrhosis, alcoholism, or currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
  4. Any anti-tumor therapy including chemotherapy and radiotherapy within 3 weeks prior to the first dose of study drug
  5. Receipt of small molecule targeted therapy with approved anti-tumor therapy within 7 days or approximately 5 half-lives (whichever is longer) prior to the first dose of study drug
  6. Any monoclonal antibody used for anti-tumor therapy within 4 weeks or 2 half-lives prior to the first dose of study drug, whichever is longer
  7. Prior use of any anti-tumor vaccine
  8. Prior administration of radioimmunotherapy within 3 months prior to the first dose of study drug
  9. Any uncontrolled active infection
  10. History of drug-induced interstitial pneumonia

Sites / Locations

  • Henan Cancer HospitalRecruiting
  • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and TechnologyRecruiting
  • First Affiliated Hospital of Soochow UniversityRecruiting
  • Chongqing university cancer hospitalRecruiting
  • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Relapsed/refractory B-NHL

Arm Description

The starting dose of HMPL-760 is initially set as 50 mg, and then the doses of 100 mg, 200 mg, 300 mg, and 400 mg are escalated successively (this dose gradient is assumed). HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.

Outcomes

Primary Outcome Measures

DLTs
Number of subjects with Dose Limiting Toxicities (DLTs) with relapsed/refractory B-cell non-Hodgkin's lymphoma relapsed/refractory B-cell non-Hodgkin's lymphoma
Safety and Tolerability
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

Secondary Outcome Measures

Objective response rate (ORR)
Defined as the proportion of patients with CR/Partial response (PR)/CR with incomplete hematologic recovery (CRi)/ partial response with lymphocytosis (PR-L)
Complete response rate (CR rate)
Defined as the proportion of patients with CR/CRi
Progression-free survival (PFS)
Defined as the time from the first dose of HMPL-760 to occurrence of Progressive disease (PD) or death, whichever comes first
Time to Response (TTR)
Defined as the time from the first dose of HMPL-760 to the first objective response
Clinical Benefit Rate (CBR)
Defined as the proportion of patients with CR/CRi, PR/PR-L and Stable disease (SD)
Duration of Response (DoR)
Defined as the time from the initial objective response to disease recurrence, progression or death
Overall Survival (OS)
Defined as the time from the first dose to death due to any cause

Full Information

First Posted
December 10, 2021
Last Updated
December 13, 2022
Sponsor
Hutchison Medipharma Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05190068
Brief Title
HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Official Title
A Multicenter, Open-label, Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-760 in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 4, 2022 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
April 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hutchison Medipharma Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
A Multicenter, Open-label, Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of HMPL-760 in Patients with Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Detailed Description
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HMPL-760 administered orally in subjects with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Patients with relapsed/refractory B-NHL, including chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular cell lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and lymphoplasmacytic/macroglobulinemia (LPL/WM).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-Cell Non-Hodgkin's Lymphoma
Keywords
B-Cell Non-Hodgkin's Lymphoma, Bruton's tyrosine kinase inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Relapsed/refractory B-NHL
Arm Type
Experimental
Arm Description
The starting dose of HMPL-760 is initially set as 50 mg, and then the doses of 100 mg, 200 mg, 300 mg, and 400 mg are escalated successively (this dose gradient is assumed). HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.
Intervention Type
Drug
Intervention Name(s)
HMPL-760
Intervention Description
HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.
Primary Outcome Measure Information:
Title
DLTs
Description
Number of subjects with Dose Limiting Toxicities (DLTs) with relapsed/refractory B-cell non-Hodgkin's lymphoma relapsed/refractory B-cell non-Hodgkin's lymphoma
Time Frame
Up to 28 days after first dose of study drug.
Title
Safety and Tolerability
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
Baseline up to the end of study
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Defined as the proportion of patients with CR/Partial response (PR)/CR with incomplete hematologic recovery (CRi)/ partial response with lymphocytosis (PR-L)
Time Frame
Baseline up to the last patient has completed 12 months after treatment
Title
Complete response rate (CR rate)
Description
Defined as the proportion of patients with CR/CRi
Time Frame
Baseline up to the last patient has completed 12 months after treatment
Title
Progression-free survival (PFS)
Description
Defined as the time from the first dose of HMPL-760 to occurrence of Progressive disease (PD) or death, whichever comes first
Time Frame
Baseline up to the last patient has completed 12 months after treatment
Title
Time to Response (TTR)
Description
Defined as the time from the first dose of HMPL-760 to the first objective response
Time Frame
Baseline up to the last patient has completed 12 months after treatment
Title
Clinical Benefit Rate (CBR)
Description
Defined as the proportion of patients with CR/CRi, PR/PR-L and Stable disease (SD)
Time Frame
Baseline up to the last patient has completed 12 months after treatment
Title
Duration of Response (DoR)
Description
Defined as the time from the initial objective response to disease recurrence, progression or death
Time Frame
Baseline up to the last patient has completed 12 months after treatment
Title
Overall Survival (OS)
Description
Defined as the time from the first dose to death due to any cause
Time Frame
Baseline up to the last patient has completed 60 months after treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed Informed Consent Form (ICF) Age ≥18 years Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2 Relapsed/refractory patients with histologically confirmed lymphoma or cytologically confirmed CLL (flow cytometry) At least one bidimensionally measurable lesion by CT with the exception of CLL, i.e., nodal lesions > 1.5 cm in maximal diameter or extranodal lesions > 1.0 cm; Expected survival longer than 24 weeks Exclusion Criteria: Patients who met any of the following criteria are excluded from the study: Lymphoma patients with central nervous system (CNS) or leptomeningeal invasion Inadequate organ function of liver and kidney Carcinoma in situ of the breast History of liver disease, including cirrhosis, alcoholism, or currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) Any anti-tumor therapy including chemotherapy and radiotherapy within 3 weeks prior to the first dose of study drug Receipt of small molecule targeted therapy with approved anti-tumor therapy within 7 days or approximately 5 half-lives (whichever is longer) prior to the first dose of study drug Any monoclonal antibody used for anti-tumor therapy within 4 weeks or 2 half-lives prior to the first dose of study drug, whichever is longer Prior use of any anti-tumor vaccine Prior administration of radioimmunotherapy within 3 months prior to the first dose of study drug Any uncontrolled active infection History of drug-induced interstitial pneumonia
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Chen, Ph.D
Phone
021-20671942
Email
Jianc2@hutch-med.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hongyuan Liao
Phone
021-20671826
Email
hongyuanl@hutch-med.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weili Zhao, Ph.D
Organizational Affiliation
Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Keshu Zhou, Ph.D
Facility Name
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guohui Cui, Ph.D
Facility Name
First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caixia Li, Ph.D
Facility Name
Chongqing university cancer hospital
City
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tao Yang, Ph.D
First Name & Middle Initial & Last Name & Degree
Yi Gong, Ph.D
Facility Name
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weili Zhao, Ph.D

12. IPD Sharing Statement

Learn more about this trial

HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

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