A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of ICP-022 in Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL)
Overview
- Phase
- Phase 1
- Intervention
- ICP-022
- Conditions
- Mantle Cell Lymphoma
- Sponsor
- Beijing InnoCare Pharma Tech Co., Ltd.
- Enrollment
- 120
- Locations
- 31
- Primary Endpoint
- overall response rate (ORR)
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The phase I/II clinical study is to investigate the safety, tolerability and pharmacokinetics/ pharmacodynamics of ICP-022.
Detailed Description
Part I: PK/PD and safety evaluation -Two regimens of ICP-022 (High dose QD and low dose BID) were designed for assessment of safety, as well as PK/PD profiles. The recommended dose of phase II clinical study will be determined according to the Part I results. Part II: Dose expansion -Anti-tumor effects of ICP-022 in Chinese patients with R/R MCL will be evaluated in approximately 80 subjects. The recommended Phase 2 dose will be used in the Part II.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women between 18 and 75 years old
- •Histologically confirmed mantle cell lymphoma (MCL), with either t(11;14) by cytogenetics and/or cyclin D1 overexpression by immunohistochemistry (IHC)
- •Subjects with refractory or relapsed mantle cell lymphoma who has received at least 1 but no more than 4 prior therapies for MCL
- •At least one measurable tumor of greater than 1.5 centimeter in long axis by contrast-enhanced CT/MRI
- •ECOG performance status of 0-2
- •Documented failure to achieve at least partial response (PR) or documented disease progression after response to, the most recent treatment regimen.
- •Subjects who meet the following laboratory parameters:
- •Absolute neutrophil count (ANC) ≥ 1.5×109/L Platelet count ≥ 75×109/L, independent of growth factor support within 7 days of the first dose with study drug, Hemoglobin ≥ 80 g/L; ANC ≥ 1.0×109/L, Platelet count ≥ 50×109/L if bone marrow involvement
- •Total bilirubin ≤ 2× ULN; AST or ALT ≤ 2.5 ULN; Creatinine clearance ≥ 30ml/min; Amylase ≤ ULN and Lipase ≤ ULN
- •International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (APTT) ≤ 1.5 ULN
Exclusion Criteria
- •History of other active malignancies within 5 years of study entry, unless cured without evidence of relapse or metastasis
- •Current or history of lymphoma involved central nervous system
- •Prior corticosteroids (at dosages equivalent to prednisone \> 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, radiation therapy, or antibody based therapies or anti-cancer TCM within 4 weeks of the start of study drug.
- •Non-hematological toxicity must recover to ≤ Grade 1 from prior anti-cancer therapy
- •Current clinically significant cardiovascular disease including:
- •Any class 3 or 4 cardiac disease such as arrhythmia, congestive heart failure or myocardial infarction defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) \< 50%
- •Primary cardiomyopathy
- •Clinical significant QTc prolong history or QTc\>470ms (female) QTc\>450ms (male)
- •Uncontrolled hypertension
- •Known active bleeding within 2 months of screening or currently taking anticoagulant/antiplatelet drugs
Arms & Interventions
High Dose of ICP-022
Two regimens of ICP-022 (High dose QD and low dose BID) are designed for study Part I to determine RP2D which will be used in Part II to further evaluate the preliminary anti-tumor effects of ICP-022 in Chinese subjects with R/R MCL.
Intervention: ICP-022
Low Dose of ICP-022
Two regimens of ICP-022 (High dose QD and low dose BID) are designed for study Part I to determine RP2D which will be used in Part II to further evaluate the preliminary anti-tumor effects of ICP-022 in Chinese subjects with R/R MCL.
Intervention: ICP-022
Outcomes
Primary Outcomes
overall response rate (ORR)
Time Frame: Up to 3 years
The efficacy measured by overall response rate (ORR) in Part II according to the 2014 International Working Group NHL
Secondary Outcomes
- Area under the concentration time curve up to the last data point above LOQ (AUC(last))(up to 4 weeks)
- Area under the concentration time curve up to the time "t" (AUC(0-t))(up to 4 weeks)
- overall survival (OS)(Up to 3 years)
- The percent of target occupancy(up to 4 weeks)
- Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I(Up to 3 years)
- Maximum plasma drug concentrations (Cmax)(up to 4 weeks)
- time to progression (TTP)(Up to 3 years)
- progression free survival (PFS)(Up to 3 years)
- Time of maximum plasma drug concentrations (Tmax)(up to 4 weeks)
- Apparent half-life for designated elimination phases (t½)(up to 4 weeks)