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

The Efficacy and Safety of Zanuburutinib in Relapsed and Refractory Idiopathic Multicentric Castleman Disease (iMCD): a Prospective, Single-center, Single-arm Trial

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

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Multicentric Castleman's Disease
• Intervention / Treatment: Drug: Zanubrutinib

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100005
      • Recruiting
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Zanuburutinib; Oral Zanuburutinib 160mg twice a day	Drug: Zanubrutinib; Oral Zanuburutinib, 160mg twice a day; Other Names: brukinsa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) at Week 12	Overall response (including partial response and complete response) rate at week 12 after zanuburutinib therapy	From date of treatment initiation to 12 weeks after treatment
Overall response rate (ORR) at Week 24	Overall response (including partial response and complete response) rate at week 24 after zanuburutinib therapy	From date of treatment initiation to 24 weeks after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Time to disease progression or death	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
Overall survival	Time to death	From date of treatment initiation until the date of death from any cause, whichever came first, assessed up to 36 months
Number of Participants With Treatment-related Adverse Events	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade)	From initiation study regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2021
• Primary Completion (ANTICIPATED): January 1, 2025
• Study Completion (ANTICIPATED): January 1, 2025

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (ACTUAL): February 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 5, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: safety; efficacy; iMCD; Zanuburutinib
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Castleman Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: ZS-2551

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No