A Study to Evaluate ICP-022 in Patients With R/R Mantle Cell Lymphoma (MCL)

Mantle Cell Lymphoma Clinical Trial

Official title:

A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of ICP-022 in Patients With Relapsed/Refractory Mantle Cell Lymphoma (MCL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03494179
• Other study ID #: ICP-CL-00102
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2, 2018
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2023
• Source: Beijing InnoCare Pharma Tech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The phase I/II clinical study is to investigate the safety, tolerability and pharmacokinetics/ pharmacodynamics of ICP-022.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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:

1. 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

2. Total bilirubin = 2× ULN; AST or ALT = 2.5 ULN; Creatinine clearance = 30ml/min; Amylase = ULN and Lipase = ULN

3. International normalized ratio (INR) = 1.5 ULN and activated partial thromboplastin time (APTT) = 1.5 ULN

• Life expectancy = 4 months

• Able to provide signed written informed consent

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

• Urine protein = 2+ and quantitation = 2g/24hours

• History of deep vein thrombosis or pulmonary embolism

• Disease significantly affecting gastrointestinal function such as dysphagia, chronic diarrhea, intestinal obstruction, or resection of the stomach

• Allogeneic stem cell transplant within 6 months prior to first dose of study drug or related active infection

• Major surgery within 6 weeks of screening, except for diagnostic test or vascular access setup

• Known active infection with HBV, HCV or HIV or any uncontrolled active systemic infection

• Any history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe lung function impairment

• Prior exposure to a BTK inhibitor,BCR pathway ingibitor(such as PI3K, SYK) or BCL-2 kinase inhibitor

• Suitable and ready for allogeneic stem cell transplant

• Inability to comply with study procedures

• Drug abuser or alcoholics

• Lactating or pregnant women, or women who will not use contraception during the study and for 180 days after the last dose of study drug if sexually active and able to bear children

• Requires treatment with moderate or strong cytochrome P450 family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

Intervention

Drug:
• ICP-022
The drug product is a white, round, uncoated tablet.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Jilin Cancer Hospital	Chang Chun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	West China Hospital,Sichuan University	Chengdu	Sichuan
China	The Second Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhengjiang University	Hangzhou	Zhejiang
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Anhui Province Cancer Hospital	Hefei	Anhui
China	Qilu Hosptial of Shandong University	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Xin Hua Hospital Affiated to Shanghai Jiao Tong University School of Medicin	Shanghai	Shanghai
China	Zhongshan Hospital	Shanghai	Shanghai
China	Liaoning Cancer Hospital and Institute	Shenyang	Liaoning
China	The First Hospital of China Medical University	Shenyang	Liaojing
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital	Wuhan	Hubei
China	Wuhan Union Hospital	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Henan Provincial People's Hospital	Zhengzhou	Henan
China	Henan Tumor Hospital	Zhengzhou	Henan
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing InnoCare Pharma Tech Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate (ORR)	The efficacy measured by overall response rate (ORR) in Part II according to the 2014 International Working Group NHL	Up to 3 years
Secondary	Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I	The safety of ICP-022 measured by the occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I	Up to 3 years
Secondary	time to progression (TTP)	The efficacy measured by time to progression (TTP) in Part II	Up to 3 years
Secondary	progression free survival (PFS)	The efficacy measured by progression free survival (PFS) in Part II	Up to 3 years
Secondary	overall survival (OS)	The efficacy measured by overall survival (OS) in Part II	Up to 3 years
Secondary	Area under the concentration time curve up to the time "t" (AUC(0-t))	Area under the concentration time curve up to the time "t" (AUC(0-t)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Secondary	The percent of target occupancy	PBMC from individual subject before and after dosing will be collected and the target occupancy will be determined by ELISA. The percent of target occupancy will be compared descriptively.	up to 4 weeks
Secondary	Maximum plasma drug concentrations (Cmax)	Individual plasma concentrations of ICP-022 will be measured and Cmax will be calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Secondary	Time of maximum plasma drug concentrations (Tmax)	Time of maximum plasma drug concentrations (Tmax) of ICP-022 will be recorded.	up to 4 weeks
Secondary	Apparent half-life for designated elimination phases (t½)	Apparent half-life for designated elimination phases (t½) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks
Secondary	Area under the concentration time curve up to the last data point above LOQ (AUC(last))	Area under the concentration time curve up to the last data point above LOQ (AUC(last)) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.	up to 4 weeks