Clinical trial NCT03797456: A Study to Evaluate ICP-022 in Patients With R/R Marginal Zone Lymphoma (MZL)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MZL
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-01-09
Enrollment: 111
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I
timeFrame: Up to 3 years
measure: Progressioin free survival (PFS)
timeFrame: Up to 3 years
measure: Duration of Response (DR)
timeFrame: Up to 3 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Area under the concentration time curve up to the time "t" (AUC(0-t))
timeFrame: up to 4 weeks
measure: Maximum plasma drug concentrations (Cmax)
timeFrame: up to 4 weeks
measure: Time of maximum plasma drug concentrations (Tmax)
timeFrame: up to 4 weeks
measure: Apparent half-life for designated elimination phases (t½)
timeFrame: up to 4 weeks
measure: Area under the concentration time curve up to the last data point above LOQ (AUC(last))
timeFrame: up to 4 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: Anhui Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Chinese People's Liberation Army General Hospital Fifth Medical Center
state: Beijing
city: Beijing
country: China
facility: Peking university People's Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Union Hospital Affiliated to Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: The Second Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Cancer Hospital Affiliated to Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Hematology Hospital, Chinese Academy of Medical Sciences
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang University Medical School affiliated to the first Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Zhu, PhD
role: PRINCIPAL_INVESTIGATOR
References: