Clinical trial NCT03493217: A Study to Evaluate ICP-022 in Patients With CLL/ SLL
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: CLL/SLL
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-04-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The phase I/II clinical study is to investigate the safety, tolerability and efficacy of ICP-022 in R/R CLL/SLL patients.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 1.Objective 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
timeFrame: Up to 3 years
measure: TTR
timeFrame: Up to 3 years
measure: TTP
timeFrame: Up to 3 years
measure: PFS
timeFrame: Up to 3 years
measure: DOR
timeFrame: Up to 3 years
measure: OS
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Province Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Chang Chun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Dalian
country: China
facility: The second affiliated hospital of dalian medical university
state: Liaoning
city: Jinan
country: China
facility: Qilu Hosptial of Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Xinhua hospital affiliated to medical college of Shanghai jiao tong university
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital,Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: The Chinese Academy of Medical Sciences Hematology Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Second affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jianyong Li, MD
role: PRINCIPAL_INVESTIGATOR
References: