A Study to Evaluate ICP-022 in Patients With R/R Marginal Zone Lymphoma (MZL)

MZL Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03797456
• Other study ID #: ICP-CL-00104
• Status: Completed
• Phase: Phase 2
• Start date: April 1, 2019
• Est. completion date: February 6, 2024

Study information

• Verified date: April 2024
• Source: Beijing InnoCare Pharma Tech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Safety, tolerability evaluation, and anti-tumor effects of ICP-022 in Chinese patients with R/R MZL will be evaluated in approximately 110 subjects. Pharmacokinetics of ICP-022 will be evaluated in approximately 20 subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: February 6, 2024
• Est. primary completion date: December 27, 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 marginal zone lymphoma (MZL), and at least one measurable tumor of greater than 1.5 centimeter outside of the spleen

• Subjects with refractory or relapsed MZL who has received at least 1 but no more than 4 prior therapies for MZL

• 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 have indications for treatment (threatened end-organ function, bulky disease >5cm, symptoms, steady progression, wish to treat)

• Subjects 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 = 75 g/L; ANC = 1.0×109/L, Platelet count = 50×109/L, Hemoglobin = 50 g/L; if bone marrow involvement

2. Total bilirubin = 1.5× ULN; AST or ALT = 2× ULN; Creatinine = 1.5× ULN; Amylase = ULN and Lipase = ULN

3. International normalized ratio (INR) = 1.5 ULN

• Life expectancy = 3 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 (except for 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

• 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

• Toxicity must be recovered to = Grade 1 from prior anti-cancer therapy

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

• Prior organ or hematopoietic stem cell transplant

• 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 or BCR pathway inhibitor (PI3K or Syk) and BCL-2 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, B-Cell, Marginal Zone
• MZL

Intervention

Drug:
• ICP-022
ICP-022 (tablets, 50 mg) is given orally at the dose of 150 mg/day from day 1 to day 28 of each cycle for up to a total of 6 cycles or until progression.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Chinese People's Liberation Army General Hospital Fifth Medical Center	Beijing	Beijing
China	Peking university People's Hospital	Beijing	Beijing
China	First Hospital of Jilin University	Changchun	Jilin
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Union Hospital Affiliated to Fujian Medical University	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Affiliated Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Zhejiang University Medical School affiliated to the first Hospital	Hangzhou	Zhejiang
China	Affiliated Cancer Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Anhui Cancer Hospital	Hefei	Anhui
China	Anhui Provincial Hospital	Hefei	Anhui
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	The Second Hospital of Lanzhou University	Lanzhou	Gansu
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Jiangsu Provincial People's Hospital	Nanjing	Jiangsu
China	Cancer Hospital Affiliated to Fudan University	Shanghai	Shanghai
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Hematology Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan
China	Henan Provincial People's 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	Progressioin free survival (PFS)	Progression free survival (PFS) is defined as the time from registration to the first occurrence of progression or relapse as assessed by the investigator, or death from any cause. PFS for patients without disease progression, relapse, or death will be censored at the time of the last tumor assessment.	Up to 3 years
Secondary	Duration of Response (DR)	Duration of response as defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause. Patients alive without progression and relapse will be censored at the latest tumor assessment date or the stopping date.	Up to 3 years
Secondary	Overall survival (OS)	Overall survival is defined as the period from the induction registration to death from any cause. Patients who have not died until the time of the analysis will be censored at their last contact date.	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	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