A Study to Evaluate ICP-022 in Patients With CLL/ SLL

CLL/SLL Clinical Trial

Official title:

A Multicenter, Open-label Study to Evaluate the Safety and Efficacy of ICP-022 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03493217
• Other study ID #: ICP-CL-00103
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 17, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: June 2022
• 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 efficacy of ICP-022 in R/R CLL/SLL patients.

Description:

Part I: Safety evaluation -2 regimens of ICP-022 (High and low dose QD) are designed for safety assessment. 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 CLL/SLL 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: 100
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women with the age more than 18 years

• Subjects with confirmed diagnosis of CLL/SLL following IWCLL2008 criteria

• Refractory or relapsed CLL/SLL who have received at least one prior therapy

• At least two measurable tumors 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.There are medicalrecords confirming that the disease has not responded to the mostrecent treatment (complete and partial remission) or that thedisease has progressed after remission

• Subjects who meet the following laboratory parameters:

• Absolute neutrophil count (ANC) = 0.75×109/L, Platelet count = 50×109/L independent of growth factor support within 7 days of the first dose of study drug

• Total bilirubin = 2× ULN (unless due to Gilbert's syndrome); AST or ALT = 2.5 ULN; Creatinine = 1.5 ULN; Amylase = 1.5 ULN

• 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

• Any history of Richter's transformation

• 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 be recovered to = Grade 1 from prior anti-cancer therapy (except alopecia)

• 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

• Subjects with active bleeding within 2 months of study start 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

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

• Prior organ or allogeneic hematopoietic stem cell transplant within 6 months prior to first dose of study drug

• 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 or PI3K, SYK, bcl-2 inhibitors

• History of stroke or intracranial hemorrhage within 6 months prior to enrollment

• Any mental or cognitive disorder, unable to understand and comply with the requirements of the study

• Drug abuser or alcoholics

• Lactating or pregnant women, or women who will not agree to 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

• CLL/SLL

Intervention

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

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University People's 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 affiliated 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	Second affiliated hospital of medical college of zhejiang university	Hangzhou	Zhejiang
China	The Second Affiliated Hospital Zhejiang University School of Medicine	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	Xinhua hospital affiliated to medical college of Shanghai jiao tong university	Shanghai	Shanghai
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The Chinese Academy of Medical Sciences Hematology Hospital	Tianjin	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
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

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	1.Objective response rate (ORR)	The efficacy measured by overall response rate (ORR) in Part II. Efficacy was evaluated by researchers according to IWCLL2008standard and update standard (Hallek, 2012), which was defined as complete remission (CR) of CLLsubjects, complete remission with incomplete bone marrow recovery (CRi), or partial remission (PR),including nodular partial remission (nPR) and partial remission with lymphocytosis (pr-l).SLL subjectsachieved complete response (CR) or partial response (PR).	Up to 3 years
Secondary	Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria	The safety and tolerability 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	TTR	The efficacy measured by time to response (TTR) in Part II	Up to 3 years
Secondary	TTP	The efficacy measured by time to progression (TTP) in Part II	Up to 3 years
Secondary	PFS	The efficacy measured by progression free survival (PFS) in Part II	Up to 3 years
Secondary	DOR	The efficacy measured by duration of response (DOR) in Part II	Up to 3 years
Secondary	OS	The efficacy measured by overall survival (OS) in Part II	Up to 3 years