B-Cell Non-Hodgkin's Lymphoma
Conditions
Keywords
B-Cell Non-Hodgkin's Lymphoma, Bruton's tyrosine kinase inhibitor
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).
Interventions
DRUGHMPL-760
HMPL-760 was administered continuously as a single agent orally every day in sequential 28-day cycles.
Sponsors
Hutchmed
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 * CLL confirmed by cytology (flow cytometry) * LPL/WM diagnosed by relevant tests including serum, bone marrow, and pathological examinations. 5. Except for CLL and WM, at least one bidimensionally measurable lesion is required by CT scan, which means the largest diameter of lymph node lesions \>1.5 cm or extranodal lesions \>1.0 cm; For lesions that cannot be well displayed by CT due to anatomical location (such as limb or soft tissue lesions), MRI measurement can be used. 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. Within 7 days or approximately 5 half-lives (whichever is longer) prior to the first dose of the investigational drug, received any corticosteroids or approved small molecule targeted anti-cancer therapies. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | Baseline up to 6 months after the last patient was enrolled | 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 6 months after the last patient was enrolled | Defined as the time from the first dose of HMPL-760 to the first objective response |
| Objective response rate (ORR) | Baseline up to 6 months after the last patient was enrolled | Defined as the proportion of patients with CR/Partial response (PR)/CR with incomplete hematologic recovery (CRi)/ partial response with lymphocytosis (PR-L) |
| Duration of Response (DoR) | Baseline up to 6 months after the last patient was enrolled | Defined as the time from the initial objective response to disease recurrence, progression or death |
| Overall Survival (OS) | Baseline up to 6 months after the last patient was enrolled | Defined as the time from the first dose to death due to any cause |
| Clinical Benefit Rate (CBR) | Baseline up to 6 months after the last patient was enrolled | Defined as the proportion of patients with CR/CRi, PR/PR-L and Stable disease (SD) |
| Complete response rate (CR rate) | Baseline up to 6 months after the last patient was enrolled | Defined as the proportion of patients with CR/CRi |
Countries
China
Outcome results
None listed