A Phase I, Open-label, Dose-escalation Study of the Safety and Pharmacokinetics of HMPL-523 in Patients With Relapsed or Refractory Mature B-cell Neoplasms
There are two stages in this study: a dose-escalation stage (stage 1) and a dose-expansion stage (stage 2). Dose-escalation stage (stage 1): The conventional 3+3 design (3 patients per dose cohort, with the potential to add additional 3 patients to the same cohort to further evaluate toxicity) will be applied for dose escalation and maximum tolerated dosage determination. Approximately 27 to 42 dose limited toxicities evaluable patients will be enrolled. The actual number of patients depends on the dose limited toxicities situation as well as the maximum tolerated dosage reached at this stage. Dosing will begin at 200mg once daily. A cycle of study treatment will be defined as 28 days of continuous dosing. Dose-expansion stage (stage 2): This phase is to further evaluate the safety, the pharmacokinetics and anti-tumor activity of HMPL-523 at recommended phase 2 dosage in approximately 190 patients with relapsed or refractory Hematologic Malignancies. In this stage, approximately 190 patients with Mature B-cell Neoplasms will be enrolled with recommended phase 2 dosage 600milligram(mg) one a day(QD) as starting dosing. The tumor types of the expansion stage are restricted to Chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), Mantle cell lymphoma (MCL), Follicular Lymphoma (FL), Diffuse large B-cell lymphoma (DLBCL), Marginal zone lymphoma (MZL)and Waldenstrom's macroglobulinemia (WM)/Lymphoplasmacytic lymphoma(LPL) Subjects will receive HMPL-523 with every 28-day treatment cycle until disease progression, death, or intolerable toxicity, whichever comes first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
134
Oral administration, once daily
BeijingCancer Hospital
Beijing, Beijing Municipality, China
Fudan University Shanghai Cancer Hospital
Shanghai, China
Dose limited toxicities evaluated with NCI CTCAE v4.03
Incidence of dose limited toxicities and associated dose of HMPL-523
Time frame: within 28 days after the first dose
Maximum plasma concentration calculated with Blood samples
Blood samples will be taken to measure the levels of study drug
Time frame: within 29 days after the first dose
Time to reach maximum concentration calculated with Blood samples
Blood samples will be taken to measure the levels of study drug
Time frame: within 29 days after the first dose
Objective response rate
the proportion of subjects who have a Complete Response or Partial Response
Time frame: within 30 days after the last dose
Adverse events evaluated by NCI CTCAE v4.03
Incidence of adverse events and associated dose of HMPL-523
Time frame: from the first dose to within 30 days after the last dose
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