Clinical trial NCT04743687: Zanuburutinib in Relapsed and Refractory iMCD: a Prospective, Single-center, Single-arm Trial
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Idiopathic Multicentric Castleman's Disease
Keywords: iMCD
Zanuburutinib
efficacy
safety
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-02-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This will be a single center, single arm, phase 2 study.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall response rate (ORR) at Week 12
timeFrame: From date of treatment initiation to 12 weeks after treatment
measure: Overall response rate (ORR) at Week 24
timeFrame: From date of treatment initiation to 24 weeks after treatment
Secondary outcomes:
measure: Progression free survival
timeFrame: 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
measure: Overall survival
timeFrame: From date of treatment initiation until the date of death from any cause, whichever came first, assessed up to 36 months
measure: Number of Participants With Treatment-related Adverse Events
timeFrame: From initiation study regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: