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

February 5, 2021 updated by: Peking Union Medical College Hospital

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
From date of treatment initiation to 12 weeks after treatment
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
From date of treatment initiation to 24 weeks after treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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 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
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
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)
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking Union Medical College Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2021

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2025

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 3, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2021

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 8, 2021

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 9, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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