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

Sponsor
Beijing InnoCare Pharma Tech Co., Ltd. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03494179
Collaborator
(none)
120
Enrollment
31
Locations
2
Arms
57
Anticipated Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Apr 2, 2018
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: High Dose of ICP-022

Two regimens of ICP-022 (High dose QD and low dose BID) are designed for study Part I to determine RP2D which will be used in Part II to further evaluate the preliminary anti-tumor effects of ICP-022 in Chinese subjects with R/R MCL.

Drug: ICP-022
The drug product is a white, round, uncoated tablet.
Experimental: Low Dose of ICP-022

Two regimens of ICP-022 (High dose QD and low dose BID) are designed for study Part I to determine RP2D which will be used in Part II to further evaluate the preliminary anti-tumor effects of ICP-022 in Chinese subjects with R/R MCL.

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

Outcome Measures

Primary Outcome Measures

  1. overall response rate (ORR) [Up to 3 years]

    The efficacy measured by overall response rate (ORR) in Part II according to the 2014 International Working Group NHL

Secondary Outcome Measures

  1. Occurrence of adverse events and serious adverse events according to NCI-CTCAE 4.03 grading criteria in Part I [Up to 3 years]

    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

  2. time to progression (TTP) [Up to 3 years]

    The efficacy measured by time to progression (TTP) in Part II

  3. progression free survival (PFS) [Up to 3 years]

    The efficacy measured by progression free survival (PFS) in Part II

  4. overall survival (OS) [Up to 3 years]

    The efficacy measured by overall survival (OS) in Part II

  5. Area under the concentration time curve up to the time "t" (AUC(0-t)) [up to 4 weeks]

    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.

  6. The percent of target occupancy [up to 4 weeks]

    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.

  7. Maximum plasma drug concentrations (Cmax) [up to 4 weeks]

    Individual plasma concentrations of ICP-022 will be measured and Cmax will be calculated with noncompartmental analysis using WinNonlin.

  8. Time of maximum plasma drug concentrations (Tmax) [up to 4 weeks]

    Time of maximum plasma drug concentrations (Tmax) of ICP-022 will be recorded.

  9. Apparent half-life for designated elimination phases (t½) [up to 4 weeks]

    Apparent half-life for designated elimination phases (t½) of ICP-022 will be measured and calculated with noncompartmental analysis using WinNonlin.

  10. Area under the concentration time curve up to the last data point above LOQ (AUC(last)) [up to 4 weeks]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Anhui Province Cancer Hospital Hefei Anhui China 230009
2 Peking University Third Hospital Beijing Beijing China 100191
3 Peking Union Medical College Hospital Beijing Beijing China 100730
4 Beijing Cancer Hospital Beijing Beijing China 102206
5 Fujian Medical University Union Hospital Fuzhou Fujian China 350001
6 The First Affiliated Hospital of Xiamen University Xiamen Fujian China 361003
7 Sun Yat-sen University Cancer Center Guangzhou Guangdong China 510060
8 Guangzhou First People's Hospital Guangzhou Guangdong China 510180
9 The Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China 050011
10 Henan Provincial People's Hospital Zhengzhou Henan China 450003
11 Henan Tumor Hospital Zhengzhou Henan China 450008
12 The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China 450052
13 Wuhan Union Hospital Wuhan Hubei China 430022
14 Tongji Hospital Wuhan Hubei China 430030
15 Jiangsu Province Hospital Nanjing Jiangsu China 210029
16 Jilin Cancer Hospital Chang Chun Jilin China 130012
17 The First Hospital of Jilin University Changchun Jilin China 130021
18 The First Hospital of China Medical University Shenyang Liaojing China 110001
19 The Second Hospital of Dalian Medical University Dalian Liaoning China 116044
20 Liaoning Cancer Hospital and Institute Shenyang Liaoning China 110042
21 Qilu Hosptial of Shandong University Jinan Shandong China 250012
22 Shandong Provincial Hospital Jinan Shandong China 250021
23 The Affiliated Hospital of Qingdao University Qingdao Shandong China 266071
24 Zhongshan Hospital Shanghai Shanghai China 200032
25 Xin Hua Hospital Affiated to Shanghai Jiao Tong University School of Medicin Shanghai Shanghai China 200092
26 West China Hospital,Sichuan University Chengdu Sichuan China 610041
27 Tianjin Medical University Cancer Institute and Hospital Tianjin Tianjin China 300060
28 The First Affiliated Hospital of Zhengjiang University Hangzhou Zhejiang China 310003
29 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
30 The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China 310052
31 The First Affiliated Hospital of Wenzhou Medical University Wenzhou Zhejiang China 325000

Sponsors and Collaborators

  • Beijing InnoCare Pharma Tech Co., Ltd.

Investigators

  • Principal Investigator: Jun Zhu, PhD, Peking University Cancer Hospital & Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Beijing InnoCare Pharma Tech Co., Ltd.
ClinicalTrials.gov Identifier:
NCT03494179
Other Study ID Numbers:
  • ICP-CL-00102
First Posted:
Apr 11, 2018
Last Update Posted:
Jul 6, 2022
Last Verified:
Jun 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell

Study Results

No Results Posted as of Jul 6, 2022