This is a Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies.
This is an open-label, multi-center Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies. This study includes 2 parts: Part A is the dose escalation part of the study, and Part B is the dose expansion part of the study. In Part A, patients were enrolled using accelerated titration design for the first three single patient cohorts and 3+3 dose escalation design for the rest cohorts. The starting dose of MH048 in soft gel capsule form was 5 mg/day QD. Cycle length will be 28 days. In Part B, the dose and lymphoma subtypes for expansion phase will depend on the results from Part A.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
57
Soft gel capsules 5 mg and 25 mg,oral MH048 should be administered after an overnight fast.
the First Affiliated Hospita,Medicine School of Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGTo evaluate the incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability]
Assess incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0
Time frame: Up to approximately 24 Months
To determine the MTD of MH048
If 2 or more treated subjects at a dose level experience a DLT before Day 28, dose escalation will stop and the prior dose level will be considered the MTD for that schedule.
Time frame: At the end of Cycle 1( 28 day) of each dose escalation cohort.
To establish the RP2D.
The determination of RP2D for phase 2 according to the result of dose expansion cohorts.
Time frame: Up to approximately 24 Months
Characterization of Pharmacokinetics (Cmax)
Maximum drug concentration (Cmax)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (AUC)
Area Under the Curve (AUC)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (CL)
Clearance (CL)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (t1/2)
Elimination half-life (t1/2)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Preliminary evidence of anti-tumor activity, in terms of Objective Response Rate (ORR)
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The number (%) of subjects with best overall response (BoR) of CR or PR.
Time frame: From date of enrollment until the date of best overall response (BoR) of CR or PR, assessed up to approximately 24 months.
Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR)
The duration from the first documentation of CR or PR to the first documented PD or death due to any cause, whichever occurs first.
Time frame: From the first documented of CR or PR to the first documented PD or death due to any cause, whichever came first, , assessed up to approximately 24 months.