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

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Primary Purpose

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Bortezomib

Cyclophosphamide

Dexamethason

About this trial

This is an interventional treatment trial for Idiopathic Multicentric Castleman's Disease focused on measuring Idiopathic Multicentric Castleman's Disease, BCD Regimen, Efficacy, Safety

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Demography: ≥18 years, all race/ethnic groups in China;
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);
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;
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;
Informed consent must be signed.

Exclusion Criteria:

age under 18 years;
Immunosuppressive or anti-neoplastic drugs within the last 3 months;
serious diseases including malignancy;
Plan to have babies within 1 year after enrollment (for women and men), or pregnancy / breast-feeding (for women);
Known hypersensitivity to study agents;
Active infection requiring systemic treatment;
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;
Unwilling or unable to provide informed consent;
Unwilling to return for follow-up at PUMCH.

Sites / Locations

Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BCD regimen

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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;

Progression-free survival (PFS)

defined as the time to disease PD

Overall survival (OS)

defined as the time to patients' death

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.

Change in hemoglobin level

hemoglobin with g/L as unit of measure

Change in IL-6 (interleukin-6)

IL-6 level with pg/ml as unit of measure

Change in CRP

CRP (c-reactive protein) level with mg/L as unit of measure

Change in ESR

ESR (eerythrocyte sedimentation rate) level with mm/h as unit of measure

Change in IgG level

IgG (immunoglobin G) level with g/L as unit of measure

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.

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)

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)

Full Information

NCT ID

NCT03982771

First Posted

May 3, 2019

Last Updated

June 9, 2019

Sponsor

Peking Union Medical College Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03982771

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Unknown status

Study Start Date

January 1, 2019 (Actual)

Primary Completion Date

January 1, 2022 (Anticipated)

Study Completion Date

January 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Idiopathic Multicentric Castleman's Disease

Keywords

Idiopathic Multicentric Castleman's Disease, BCD Regimen, Efficacy, Safety

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

This will be a single center, single arm, phase-II pilot study.

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

BCD regimen

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Intervention Description

-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;

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

-Cyclophosphamide: (oral) 300mg/m2 on Day 1, 8, 15, 22 every month for 9 months;

Intervention Type

Drug

Intervention Name(s)

Dexamethason

Intervention Description

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.

Primary Outcome Measure Information:

Title

Overall response

Description

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.

Time Frame

12 months after the last patient begins study treatment.

Secondary Outcome Measure Information:

Title

Time to initial response

Description

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

Time Frame

12 months after the last patient begins study treatment.

Title

Time to best response

Description

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;

Time Frame

12 months after the last patient begins study treatment.

Title

Progression-free survival (PFS)

Description

defined as the time to disease PD

Time Frame

12 months after the last patient begins study treatment.

Title

Overall survival (OS)

Description

defined as the time to patients' death

Time Frame

12 months after the last patient begins study treatment.

Title

Change in PHQ-9 score

Description

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.

Time Frame

From Day 1 of the BCD treatment until 12 months after the treatment

Title

Change in hemoglobin level

Description

hemoglobin with g/L as unit of measure

Time Frame