Brief Title
HMPL-760 Safety and Tolerability Study in Patients With Previously Treated CLL/SLL or NHL
Official Title
A Multicenter, Open-label, Phase 1 Study Evaluating the Safety and Tolerability of HMPL-760 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Other Non-Hodgkin Lymphoma (NHL)
Brief Summary
An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and
preliminary efficacy of HMPL-760 in patients with previously treated CLL/SLL or NHL
Detailed Description
HMPL-760 is a highly potent, selective, and reversible inhibitor against BTK, which would be
studied in B-cell malignancy carrying either BTK(WT) or BTK(C481S).
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety,
tolerability, PK, PD, and preliminary efficacy of HMPL-760 in patients with previously
treated CLL/SLL or NHL
The study consists of 2 parts:
Part 1- Dose Escalation to determine MTD and/or RP2D of HMPL-760
Part 2- Dose Expansion to characterize the safety and tolerability of HMPL-760
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence of DLTs
Secondary Outcome
Objective Response Rate (ORR)
Condition
CLL/SLL
Intervention
HMPL-760
Study Arms / Comparison Groups
Treatment
Description: All patients to receive HMPL-760 daily.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
168
Start Date
February 15, 2022
Completion Date
October 30, 2025
Primary Completion Date
April 30, 2025
Eligibility Criteria
Inclusion Criteria:
- ECOG performance status of 0 or 1;
- Histologically confirmed NHL or CLL with disease progression or intolerance to either
≥2 prior regimens. Patients with CLL/SLL and indolent NHL must meet criteria for
systemic therapy. Patients with gastric extranodal MZL who are H. pylori positive must
have failed H. pylori eradication therapy.
- Availability of tumor sample: This may be an archival tissue sample obtained after
most recent therapy or a fresh biopsy; if tumor sample is not available for patients
in dose escalation, the Sponsor may waive the requirement after discussion.
- Dose expansion stage only: Patients must have been treated with 1 prior regimen
containing a BTK inhibitor in cohorts 1 to 5;
- Expected survival of more than 24 weeks as determined by the Investigator.
Exclusion Criteria:
- Patients with primary central nervous system lymphoma.
- Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) <0.75×109/L
- Hemoglobin <8 mg/L
- Platelets <50×109/L
- Note: In the dose expansion stage, patients with cell counts below the thresholds
listed above may be considered eligible if there is documented bone marrow
infiltration and Sponsor approval
- Inadequate organ function
- International normalized ratio (INR) >1.5×ULN, activated partial thromboplastin time
(aPTT) >1.5×ULN
- Patients requiring anticoagulation therapy (except vitamin K antagonists [ie,
warfarin]) but with a stable INR within the recommended range according to the local
guideline are eligible.
- Patients with presence of second primary malignant tumors within the last 2 years,
with the exception of the following:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Clinically significant history of liver disease, including cirrhosis or current known
active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV),
hepatitis C virus (HCV), or cytomegalovirus (CMV).
- Cancer therapy, including chemotherapy, hormonal therapy, biologic therapy, vaccine,
or radiotherapy within 3 weeks prior to initiation of study treatment. For oral
targeted therapies, a washout period of 5 half-lives of the agent (minimum 3 days)
prior to the initiation of study treatment can be used.
- Any granulocyte colony-stimulating factor treatment/blood transfusion within 7 days
before the screening hematology test.
- Prior use of any drug that is a strong inducer or inhibitor of CYP3A4 within 2 weeks
prior to initiation of study treatment.
- Prior use of proton pump inhibitors (PPIs) within 5 days of study treatment
- Any transplant within 100 days prior to initiation of study treatment
- Clinically significant active infection or with an unexplained fever.
- Treatment within a clinical study of an investigational agent or using an
investigational device within 3 weeks prior to initiation of the current study
treatment.
- AEs from prior antineoplastic therapy that have not resolved to grade <1
- Pregnant (positive urine or serum beta human chorionic gonadotropin test) or lactating
women.
- New Your Heart Association (NYHA) class II or greater congestive heart failure.
NOTE: Only key inclusion/exclusion criteria are listed. Full details are in the protocol.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Vijay Jayaprakash, MBBS, PHD, 973-421-5002, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05176691
Organization ID
2021-760-GLOB1
Responsible Party
Sponsor
Study Sponsor
Hutchison Medipharma Limited
Study Sponsor
Vijay Jayaprakash, MBBS, PHD, Study Director, Hutchison Medipharma Limited
Verification Date
February 2022