BCD Regimen in Newly Diagnosed Idiopathic Multicentric Castleman's Disease (iMCD)

Bortezomib, Cyclophosphamide and Dexamethasone (BCD) in Newly Diagnosed Idiopathic Multicentric Castleman's Disease (iMCD) : a Prospective, Single-center, Single-arm, Phase-II Pilot Trial

To explore the effectiveness and safety of bortezomib, cyclophosphamide and dexamethasone (BCD regimen) in newly diagnosed idiopathic Multicentric Castleman's disease (iMCD) patients.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Multicentric Castleman's Disease
• Intervention / Treatment: Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethason

Detailed Description

This will be a single center, open-labeled, single arm, phase-II pilot study. The treatment and the response evaluation phase will last from the time of enrollment up to 21 months (evaluation will be carried out every 3 months in the first 9 months and every 6 months from Month 9 to Month 21). The maintenance and follow-up phase to assess for progression of disease will last from 21 months to 45 months after enrollment (evaluation will be carried out every 12 months). 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:

1. Demography: ≥18 years, all race/ethnic groups in China;
2. Newly diagnosed and previously untreated (patients are allowed to have received oral prednisone for up to 1 week before enrollment) symptomatic iMCD patients (symptomatic disease is defined by the presence of clinical symptoms with the NCI-CTCAE grading ≥1 that are attributable to the disease, and for which treatment is indicated; iMCD diagnosis is based on the international consensus diagnostic criteria);
3. Clinical laboratory values meeting these criteria at screening: absolute neutrophil count ≥ 1·0 x 109/L, Platelets ≥ 50 x 109/L, Alanine aminotransferase (ALT) within 2·5 x upper limit of normal (ULN); total bilirubin within 2·5 x ULN; estimated glomerular filtration rate (according to MDRD formula) <15ml/min;
4. Women of childbearing potential must agree to use birth control measures during the study and for at least 3 months after receiving the last dose of study agent, and must have a negative pregnancy test at screening period. Men must agree to use birth control measures during the study and for at least 3 months after receiving the last dose of study agent;
5. Informed consent must be signed.

Exclusion Criteria:

1. age under 18 years;
2. Immunosuppressive or anti-neoplastic drugs within the last 3 months;
3. serious diseases including malignancy;
4. Plan to have babies within 1 year after enrollment (for women and men), or pregnancy / breast-feeding (for women);
5. Known hypersensitivity to study agents;
6. Active infection requiring systemic treatment;
7. Other severe concurrent disease (eg. uncontrolled diabetes, symptomatic coronary heart disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study;
8. Unwilling or unable to provide informed consent;
9. Unwilling to return for follow-up at PUMCH.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BCD regimen; Bortezomib, cyclophosphamide and dexamethasone (the BCD regimen) would be utilized in newly diagnosed iMCD (idiopathic Multicentric Castleman's disease) patients

Drug: Bortezomib; -Bortezomib: 1.3mg/m2 subcutaneous injection on Day 1,8,15,22 every month for 9 months; And maintained with 1.3mg/m2 subcutaneous injection every two weeks from Month 9 to 21; Drug: Cyclophosphamide; -Cyclophosphamide: (oral) 300mg/m2 on Day 1, 8, 15, 22 every month for 9 months; Drug: Dexamethason; Dexamethasone: (oral) 40mg on Day 1,8,15,22 every month for 9 months; and maintained with 20mg (oral) every two weeks from Month 9 to 21.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response	Overall response is composed by biochemical, lymph node and symptom response, is the primary outcome of this study. According to the CDCN response criteria, an overall CR (complete response) requires a complete biochemical, lymph node, and symptomatic response; and overall PR (partial response) requires nothing less than a PR across all categories, but not meeting criteria for CR; an overall SD (stable disease) requires no PD (progression disease) in any of the categories and not meeting the criteria for CR or PR; an overall PD occurs when any category has a PD.	12 months after the last patient begins study treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to initial response	defined as the time to achieve the first PR or CR. This outcome can be further divided into time to initial overall response, time to initial symptomatic response, time to initial biochemical response, time to initial lymph node response	12 months after the last patient begins study treatment.
Time to best response	defined as the time to achieve the best response (either PR or CR). This outcome can be further divided into time to best overall response, time to best symptomatic response, time to best biochemical response, time to best lymph node response;	12 months after the last patient begins study treatment.
Progression-free survival (PFS)	defined as the time to disease PD	12 months after the last patient begins study treatment.
Overall survival (OS)	defined as the time to patients' death	12 months after the last patient begins study treatment.
Change in PHQ-9 score	PHQ-9 score (Patient Health Questionnaire scale-9) is a nine-item self-administered instrument to assess depressive symptoms which incorporates the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) classification for major depressive disorder. Each item is scored 0 - 3, which results in a range of scores between 0 and 27. PHQ-9 scores are interpreted as follows: (1) score <5, no depression; (2) score 5 - 9, mild depression; (3) score 10 - 14, moderate depression; (4) score 15 - 19, moderately severe depression; and (5) score 20 - 27,severe depression.	From Day 1 of the BCD treatment until 12 months after the treatment
Change in hemoglobin level	hemoglobin with g/L as unit of measure	From baseline until 12 months after the treatment
Change in IL-6 (interleukin-6)	IL-6 level with pg/ml as unit of measure	From baseline until 12 months after the treatment
Change in CRP	CRP (c-reactive protein) level with mg/L as unit of measure	From baseline until 12 months after the treatment
Change in ESR	ESR (eerythrocyte sedimentation rate) level with mm/h as unit of measure	From baseline until 12 months after the treatment
Change in IgG level	IgG (immunoglobin G) level with g/L as unit of measure	From baseline until 12 months after the treatment
Change in MCD-related overall symptom score	Change of MCD symptom scores. MCD symptom score (MCD disease related overall symptom score) is a 34-item score based on NCI-CTCAE (V4.0) adverse events. Each item is scored 0-5, which results in a range of scores between 0 and 170. More scores indicate more severe disease activity.	From baseline until 12 months after the treatment
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 ( ≥1 grade)	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (patients with grades ≥1 would be included)	12 months after the last patient begins study treatment.
Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 ( ≥3 grade)	Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)	12 months after the last patient begins study treatment

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: May 3, 2019
• First Submitted That Met QC Criteria: June 9, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Actual): June 12, 2019
• Last Update Submitted That Met QC Criteria: June 9, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Idiopathic Multicentric Castleman's Disease; BCD Regimen; Efficacy
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Castleman Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Bortezomib
• Other Study ID Numbers: ZS-1892

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
• product manufactured in and exported from the U.S.: No