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

• ClinicalTrials.gov Identifier: NCT04743687
• Recruitment Status: Recruiting
• First Posted: February 8, 2021
• Last Update Posted: February 9, 2021
• Sponsor: Peking Union Medical College Hospital
• Information provided by (Responsible Party): Peking Union Medical College Hospital

Study Description

Brief Summary:

To explore the effectiveness and safety of Zanuburutinib in relapsed and refractory idiopathic Multicentric Castleman's disease (iMCD) patients.

Condition or disease	Intervention/treatment	Phase
Idiopathic Multicentric Castleman's Disease	Drug: Zanubrutinib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention 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.
• Primary Purpose: Treatment
• Official Title: The Efficacy and Safety of Zanuburutinib in Relapsed and Refractory Idiopathic Multicentric Castleman Disease (iMCD): a Prospective, Single-center, Single-arm Trial
• Actual Study Start Date: January 1, 2021
• Estimated Primary Completion Date: January 1, 2025
• Estimated Study Completion Date: January 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Zanuburutinib; Oral Zanuburutinib 160mg twice a day	Drug: Zanubrutinib; Oral Zanuburutinib, 160mg twice a day; Other Name: brukinsa

Outcome Measures

Primary Outcome Measures :

1. Overall response rate (ORR) at Week 12 [ Time Frame: From date of treatment initiation to 12 weeks after treatment ]
   Overall response (including partial response and complete response) rate at week 12 after zanuburutinib therapy
2. Overall response rate (ORR) at Week 24 [ Time Frame: From date of treatment initiation to 24 weeks after treatment ]
   Overall response (including partial response and complete response) rate at week 24 after zanuburutinib therapy

Secondary Outcome Measures :

1. Progression free survival [ 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 ]
   Time to disease progression or death
2. Overall survival [ Time Frame: From date of treatment initiation until the date of death from any cause, whichever came first, assessed up to 36 months ]
   Time to death
3. Number of Participants With Treatment-related Adverse Events [ 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 ]
   Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Jian Li, M.D.; +86-18610852525; lijian@pumch.cn

Contact: Lu Zhang, M.D.; +86-18610728815; pumczhanglu@163.com

Locations

China, Beijing

Peking Union Medical College Hospital; Recruiting

Beijing, Beijing, China, 100005

Contact: Jian Li, M.D. +86-18610852525 lijian@pumch.cn

Contact: Lu Zhang, M.D. +86-18610728815 pumczhanglu@163.com

Sponsors and Collaborators

Peking Union Medical College Hospital

More Information

• Responsible Party: Peking Union Medical College Hospital
• ClinicalTrials.gov Identifier: NCT04743687
• Other Study ID Numbers: ZS-2551
• First Posted: February 8, 2021
• Last Update Posted: February 9, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Peking Union Medical College Hospital:

iMCD; Zanuburutinib; efficacy; safety

Additional relevant MeSH terms:

Castleman Disease; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Zanubrutinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action