HMPL-760 in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Relapsed/refractory B-NHL 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. |
Drug: HMPL-760
HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.
|
Outcome Measures
Primary Outcome Measures
- DLTs [Up to 28 days after first dose of study drug.]
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 [Baseline up to the end of study]
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Secondary Outcome Measures
- Objective response rate (ORR) [Baseline up to the last patient has completed 12 months after treatment]
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) [Baseline up to the last patient has completed 12 months after treatment]
Defined as the proportion of patients with CR/CRi
- Progression-free survival (PFS) [Baseline up to the last patient has completed 12 months after treatment]
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) [Baseline up to the last patient has completed 12 months after treatment]
Defined as the time from the first dose of HMPL-760 to the first objective response
- Clinical Benefit Rate (CBR) [Baseline up to the last patient has completed 12 months after treatment]
Defined as the proportion of patients with CR/CRi, PR/PR-L and Stable disease (SD)
- Duration of Response (DoR) [Baseline up to the last patient has completed 12 months after treatment]
Defined as the time from the initial objective response to disease recurrence, progression or death
- Overall Survival (OS) [Baseline up to the last patient has completed 60 months after treatment]
Defined as the time from the first dose to death due to any cause
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed Informed Consent Form (ICF)
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Age ≥18 years
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. In the expansion stage, ECOG performance status 0-2
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Relapsed/refractory patients with histologically confirmed lymphoma or cytologically confirmed CLL (flow cytometry)
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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;
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Expected survival longer than 24 weeks
Exclusion Criteria:
Patients who met any of the following criteria are excluded from the study:
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Lymphoma patients with central nervous system (CNS) or leptomeningeal invasion
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Inadequate organ function of liver and kidney
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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)
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Any anti-tumor therapy including chemotherapy and radiotherapy within 3 weeks prior to the first dose of study drug
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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
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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
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Prior use of any anti-tumor vaccine
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Prior administration of radioimmunotherapy within 3 months prior to the first dose of study drug
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Any uncontrolled active infection
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History of drug-induced interstitial pneumonia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henan Cancer Hospital | Zhengzhou | Henan | China | |
| 2 | Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology | Wuhan | Hubei | China | |
| 3 | First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | |
| 4 | Xinqiao Hospital of Army Medical University | Chongqing | China | ||
| 5 | Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine | Shanghai | China |
Sponsors and Collaborators
- Hutchison Medipharma Limited
Investigators
- Principal Investigator: Weili Zhao, Ph.D, Shanghai Jiao Tong University School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021-760-00CH1