Trial purpose
Cancer treatment
Tumor type
Haematological
Age
18 - 28
Clinical summary
Summary
This is a multicentre, Phase I, open-label, multiple-dose, dose escalation, first-in-human study. It is to be conducted in two sequential parts: dose escalation, followed by safety and schedule expansion. Part 1: Dose Escalation - this will follow a classic 3+3ose escalation schedule. The starting dose will be 40mg/day (once daily). The period for dose limiting toxicity (DLT) assessment is 21 days from first dose of BGB3111. Evaluation of a cohort of at least three (3) subjects completing DLT assessment at any given dose level is required prior to determining the next dose level and dose regimen for the subsequent cohort. Pharmacodynamic effect of BGB3111 on BTK inhibition will be studied in peripheral blood mononuclear cells (PBMCs) and in bone marrow and lymph nodes if available. The continuous safety evaluation will be performed by the sponsor, the coordinating investigator, and investigators. A Safety Monitoring Committee (SMC) will be established for the determination of dose levels to be administered and dose regimen during dose escalation, and will utilize the data available from the previous dose levels. In the event that a Maximal Tolerated Dose (MTD) is not identified due to paucity of DLTs, the dosing regimen used in the safety and schedule expansion will be based on pharmacodynamic studies of BTK inhibition in PBMCs, bone marrows and lymph nodes (if available). Part 2: Safety and Schedule Expansion this will evaluate the MTD (or anticipated Phase 2 dose, if no MTD defined) in a further 20 subjects. Subjects will be assigned to the MTD on a once daily schedule, or 50% MTD given twice a day, by alternate allocation. Patients in this part will undergo a lymph node and bone marrow biopsy at screening stage and before their day 3 dose – i.e. either 10-14 or 22-26 hours post dose, depending on assigned schedule for pharmacodynamic studies of BTK inhibition in lymph nodes and bone marrow in addition to that in PBMCs. This study will be considered complete once all patients have either manifested disease progression, ceased BGB3111 due to intolerance, or completed a total of 12 months of BGB3111. Patients in both parts of the study continuing to show clinical benefit at 12 months will be allowed to continue BGB3111 until disease progression or intolerance, on an extension study.
Conditions
This trial is treating people with B-Cell Non Hodgkin Lymphoma
Eligibility
Inclusion
- Aged ≥ 18 years, voluntarily consented to the study.
- WHO classification defined B-lymphoid malignancy, with the exception of Burkitt lymphoma/leukemia, plasma cell myeloma, acute lymphoblastic leukemia, lymphoblastic lymphoma, and plasmablastic lymphoma.
- Requirement for treatment in the opinion of the investigator.
- Disease which has relapsed, or is refractory, following at least one line of therapy, with no therapy of higher priority available.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Adequate hematologic function, as defined by neutrophils ≥ 1.0 x 10^9/L and platelets ≥ 50 x 10^9/L; participants with neutrophils < 1.0 x 10^9/L due to marrow infiltration are allowed to receive growth factors to bring pre-treatment neutrophils to ≥ 1.0 x 10^9/L.
- Adequate renal function, as defined by creatinine clearance of ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or as measured by nuclear medicine scan or 24 hour urine collection).
- Adequate liver function, as defined by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), and bilirubin ≤ 1.5 x ULN (unless documented Gilbert's syndrome).
- International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
- Female participants of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug: total abstinence from sexual intercourse, double-barrier contraception, IUD or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
- Male participants must not donate sperm from initial study drug administration, until 90 days after drug discontinuation.
Exclusion
- Current central nervous system (CNS) involvement by disease
- Current histologically transformed disease.
- Prior Bruton's tyrosine kinase (BTK) inhibitor treatment.
- Allogeneic stem cell transplantation within 6 months, or has active graft-versus-host disease (GVHD) requiring ongoing immunosuppression.
- Receipt of the following treatment prior to first dose of zanubrutinib: corticosteroids given with anti-neoplastic intent within 7 days, chemotherapy or radiotherapy within 2 weeks, monoclonal antibody within 4 weeks.
- Not recovered from toxicity of any prior chemotherapy to grade ≤ 1.
- History of other active malignancies within 2 years of study entry, with exception of (1) adequately treated in-situ carcinoma of cervix; (2) localized basal cell or squamous cell carcinoma of skin; (3) previous malignancy confined and treated locally (surgery or other modality) with curative intent.
- Uncontrolled systemic infection requiring parenteral anti-microbial therapy.
- Major surgery in the past 4 weeks.
- Known HIV, or active hepatitis B or hepatitis C infection (detected positive by PCR).
- Cardiovascular disease resulting in New York Heart Association function status of ≥ 3.
- Significant active renal, neurologic, psychiatric, hepatic or endocrinologic disease that in the investigator's opinion would adversely impact on his/her participating in the study.
- Inability to comply with study procedures.
- On medications which are cytochrome P450 (CYP) 3A inhibitors.
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
BeiGene Australia Pty Ltd
Scientific Title
A Phase IA, Open Label, Multiple Dose, Dose Escalation Study to Investigate the Safety and Pharmacokinetics of the BTK Inhibitor BGB-3111 in Subjects with Indolent B-Cell Lymphoid Malignancies
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