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Zanuburutinib in Relapsed and Refractory iMCD: a Prospective, Single-center, Single-arm Trial (iMCD)

Primary Purpose

Idiopathic Multicentric Castleman's Disease

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Zanubrutinib
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Multicentric Castleman's Disease focused on measuring iMCD, Zanuburutinib, efficacy, safety

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • fulfilled the CDCN (Castleman Disease Collaborative Network) diagnostic criteria of iMCD
  • relapsed or refractory disease. Relapsed = patients who ever achieved overall partial response (PR) or complete response (CR) with prior lines of therapy suffered from progressive disease (PD); refractory = iMCD patients who never achieved PR or CR with the first-line treatment but suffered from PD during treatment.
  • Eastern Cooperative Oncology Group performance status (ECOG-PS ≤ 2)
  • Neutrophil count ≥ 0.75×10^9/L, hemoglobin ≥ 70 g/L and platelet count > 30×10^9/L
  • Total bilirubin ≤ 2 x ULN (upper limit of normal), AST（aspartate aminotransferase） or ALT（Alanine aminotransferase）≤ 2.5 x ULN
  • INR （international normalized ratio) and APTT(activated partial thromboplastin time) ≤ 1.5 x ULN；eGFR>25ml/min/1.73m2
  • estimated survival ≥ 3 months
  • agree to take birth control methods during study period for women of reproductive age
  • agree to provide informed consent

Exclusion Criteria:

  • concurrent malignancies
  • prior history of receiving any kind of BTK (Bruton's tyrosine kinase) inhibitors
  • patients with SLE (systemic lupus erythematosus), HHV-8 (human herpesvirus-8) infection or POEMS syndrome
  • History of major surgery or radiation therapy within 4 weeks before initiation of study drug
  • history of myocardial infarction within 1 years
  • patient with history of heart failure (NYHA 3 or 4) would be excluded unless his LVEF(left ventricular ejection fraction) ≥ 50% within 1 months
  • primary cardiomyopathy; Qtc > 450ms for men and > 470ms for women
  • breast feeding or pregnant women
  • intolerance for oral regimen due to gastro-intestinal disorders
  • uncontrolled infection
  • positive HBV(hepatitis B virus)-DNA titers or positive HbsAg; positive HCV(hepatitis C virus)antibody; patients with HIV infection
  • patients with history of bleeding disorders
  • cerebral infarction or intracranial bleeding within 6 months
  • active bleeding disorders within 2 months
  • taking anti-platelet or anticoagulation drugs
  • taking drugs which strongly inhibit P450 CYP3A
  • patients or their relatives fail to understand the purpose of the study
  • any other conditions that the investigators consider to be not appropriate for inclusion

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zanuburutinib

Arm Description

Oral Zanuburutinib 160mg twice a day

Outcomes

Primary Outcome Measures

Overall response rate (ORR) at Week 12
Overall response (including partial response and complete response) rate at week 12 after zanuburutinib therapy
Overall response rate (ORR) at Week 24
Overall response (including partial response and complete response) rate at week 24 after zanuburutinib therapy

Secondary Outcome Measures

Progression free survival
Time to disease progression or death
Overall survival
Time to death
Number of Participants With Treatment-related Adverse Events
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)

Full Information

First Posted
February 3, 2021
Last Updated
February 5, 2021
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04743687
Brief Title
Zanuburutinib in Relapsed and Refractory iMCD: a Prospective, Single-center, Single-arm Trial
Acronym
iMCD
Official Title
The Efficacy and Safety of Zanuburutinib in Relapsed and Refractory Idiopathic Multicentric Castleman Disease (iMCD): a Prospective, Single-center, Single-arm Trial
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2021 (Actual)
Primary Completion Date
January 1, 2025 (Anticipated)
Study Completion Date
January 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To explore the effectiveness and safety of Zanuburutinib in relapsed and refractory idiopathic Multicentric Castleman's disease (iMCD) patients.
Detailed Description
This is a single center, open-labeled , single arm, prospective study which includes a safety run-in phase. The primary endpoint is the overall response rate which includes complete response (CR) and partial response (PR) at Week 12 and Week 24. The secondary endpoints include progression-free survival (PFS), overall survival (OS), and adverse events. There are two phases of the study. The first phase is the 'safety run-in phase'which plans to enroll 6 patients who would be observed for safety issues for 12 weeks after study drug administration. If no Grade ≥ 4 (CTCAE) adverse events (AE) occurs during this phase, the study would enter the second phase; if Grade ≥ 4 (CTCAE) AE happens during this phase, the study would be terminated. In the second phase of the study, another 24 patients would be enrolled. All enrolled patients would receive the study drug until progression of disease, intolerability of the drugs or Week 96 and would be followed every 4 weeks in the first 12 weeks, every 12 weeks until Week 48 and every 24 weeks until Week 96. The follow-up phase to assess PFS and OS will last from initiation of study drug to 36 months after enrollment (evaluation would be carried out every 24 weeks after Week 96). The total study duration will be 4 years after the last patient starts study medication.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Multicentric Castleman's Disease
Keywords
iMCD, Zanuburutinib, efficacy, safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This will be a single center, single arm, phase 2 study.
Masking
None (Open Label)
Masking Description
This will be an open label study.
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Zanuburutinib
Arm Type
Experimental
Arm Description
Oral Zanuburutinib 160mg twice a day
Intervention Type
Drug
Intervention Name(s)
Zanubrutinib
Other Intervention Name(s)
brukinsa
Intervention Description
Oral Zanuburutinib, 160mg twice a day
Primary Outcome Measure Information:
Title
Overall response rate (ORR) at Week 12
Description
Overall response (including partial response and complete response) rate at week 12 after zanuburutinib therapy
Time Frame
From date of treatment initiation to 12 weeks after treatment
Title
Overall response rate (ORR) at Week 24
Description
Overall response (including partial response and complete response) rate at week 24 after zanuburutinib therapy
Time Frame
From date of treatment initiation to 24 weeks after treatment
Secondary Outcome Measure Information:
Title
Progression free survival
Description
Time to disease progression or death
Time Frame
From date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Title
Overall survival
Description
Time to death
Time Frame
From date of treatment initiation until the date of death from any cause, whichever came first, assessed up to 36 months
Title
Number of Participants With Treatment-related Adverse Events
Description
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)
Time Frame
From initiation study regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: fulfilled the CDCN (Castleman Disease Collaborative Network) diagnostic criteria of iMCD relapsed or refractory disease. Relapsed = patients who ever achieved overall partial response (PR) or complete response (CR) with prior lines of therapy suffered from progressive disease (PD); refractory = iMCD patients who never achieved PR or CR with the first-line treatment but suffered from PD during treatment. Eastern Cooperative Oncology Group performance status (ECOG-PS ≤ 2) Neutrophil count ≥ 0.75×10^9/L, hemoglobin ≥ 70 g/L and platelet count > 30×10^9/L Total bilirubin ≤ 2 x ULN (upper limit of normal), AST（aspartate aminotransferase） or ALT（Alanine aminotransferase）≤ 2.5 x ULN INR （international normalized ratio) and APTT(activated partial thromboplastin time) ≤ 1.5 x ULN；eGFR>25ml/min/1.73m2 estimated survival ≥ 3 months agree to take birth control methods during study period for women of reproductive age agree to provide informed consent Exclusion Criteria: concurrent malignancies prior history of receiving any kind of BTK (Bruton's tyrosine kinase) inhibitors patients with SLE (systemic lupus erythematosus), HHV-8 (human herpesvirus-8) infection or POEMS syndrome History of major surgery or radiation therapy within 4 weeks before initiation of study drug history of myocardial infarction within 1 years patient with history of heart failure (NYHA 3 or 4) would be excluded unless his LVEF(left ventricular ejection fraction) ≥ 50% within 1 months primary cardiomyopathy; Qtc > 450ms for men and > 470ms for women breast feeding or pregnant women intolerance for oral regimen due to gastro-intestinal disorders uncontrolled infection positive HBV(hepatitis B virus)-DNA titers or positive HbsAg; positive HCV(hepatitis C virus)antibody; patients with HIV infection patients with history of bleeding disorders cerebral infarction or intracranial bleeding within 6 months active bleeding disorders within 2 months taking anti-platelet or anticoagulation drugs taking drugs which strongly inhibit P450 CYP3A patients or their relatives fail to understand the purpose of the study any other conditions that the investigators consider to be not appropriate for inclusion
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Li, M.D.
Phone
+86-18610852525
Email
lijian@pumch.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Lu Zhang, M.D.
Phone
+86-18610728815
Email
pumczhanglu@163.com
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100005
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Li, M.D.
Phone
+86-18610852525
Email
lijian@pumch.cn
First Name & Middle Initial & Last Name & Degree
Lu Zhang, M.D.
Phone
+86-18610728815
Email
pumczhanglu@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

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Zanuburutinib in Relapsed and Refractory iMCD: a Prospective, Single-center, Single-arm Trial

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