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出境医 / 临床实验 / BCD Regimen in Newly Diagnosed Idiopathic Multicentric Castleman's Disease (iMCD)

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

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.

Condition or disease Intervention/treatment Phase
Idiopathic Multicentric Castleman's Disease Drug: Bortezomib Drug: Cyclophosphamide Drug: Dexamethason Phase 2

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 Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This will be a single center, single arm, phase-II pilot study.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2023
Arms and Interventions
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.
Outcome Measures
Primary Outcome Measures :
  1. Overall response [ Time Frame: 12 months after the last patient begins study treatment. ]
    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 :
  1. Time to initial response [ Time Frame: 12 months after the last patient begins study treatment. ]
    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

  2. Time to best response [ Time Frame: 12 months after the last patient begins study treatment. ]
    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;

  3. Progression-free survival (PFS) [ Time Frame: 12 months after the last patient begins study treatment. ]
    defined as the time to disease PD

  4. Overall survival (OS) [ Time Frame: 12 months after the last patient begins study treatment. ]
    defined as the time to patients' death

  5. Change in PHQ-9 score [ Time Frame: From Day 1 of the BCD treatment until 12 months after the treatment ]
    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.

  6. Change in hemoglobin level [ Time Frame: From baseline until 12 months after the treatment ]
    hemoglobin with g/L as unit of measure

  7. Change in IL-6 (interleukin-6) [ Time Frame: From baseline until 12 months after the treatment ]
    IL-6 level with pg/ml as unit of measure

  8. Change in CRP [ Time Frame: From baseline until 12 months after the treatment ]
    CRP (c-reactive protein) level with mg/L as unit of measure

  9. Change in ESR [ Time Frame: From baseline until 12 months after the treatment ]
    ESR (eerythrocyte sedimentation rate) level with mm/h as unit of measure

  10. Change in IgG level [ Time Frame: From baseline until 12 months after the treatment ]
    IgG (immunoglobin G) level with g/L as unit of measure

  11. Change in MCD-related overall symptom score [ Time Frame: From baseline until 12 months after the treatment ]
    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.

  12. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 ( ≥1 grade) [ Time Frame: 12 months after the last patient begins study treatment. ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (patients with grades ≥1 would be included)

  13. Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 ( ≥3 grade) [ Time Frame: 12 months after the last patient begins study treatment ]
    Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations

Locations
Layout table for location information
China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100005
Contact: Jian Li, M.D.    +86-18610852525    lijian@pumch.cn   
Contact: Lu Zhang, M.D.    +86-18610728815    pumczhanglu@163.com   
Sponsors and Collaborators
Peking Union Medical College Hospital
Tracking Information
First Submitted Date  ICMJE May 3, 2019
First Posted Date  ICMJE June 12, 2019
Last Update Posted Date June 12, 2019
Actual Study Start Date  ICMJE January 1, 2019
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2019) 		Overall response [ Time Frame: 12 months after the last patient begins study treatment. ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2019)
  • Time to initial response [ Time Frame: 12 months after the last patient begins study treatment. ]
    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 [ Time Frame: 12 months after the last patient begins study treatment. ]
    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) [ Time Frame: 12 months after the last patient begins study treatment. ]
    defined as the time to disease PD
  • Overall survival (OS) [ Time Frame: 12 months after the last patient begins study treatment. ]
    defined as the time to patients' death
  • Change in PHQ-9 score [ Time Frame: From Day 1 of the BCD treatment until 12 months after the treatment ]
    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 [ Time Frame: From baseline until 12 months after the treatment ]
    hemoglobin with g/L as unit of measure
  • Change in IL-6 (interleukin-6) [ Time Frame: From baseline until 12 months after the treatment ]
    IL-6 level with pg/ml as unit of measure
  • Change in CRP [ Time Frame: From baseline until 12 months after the treatment ]
    CRP (c-reactive protein) level with mg/L as unit of measure
  • Change in ESR [ Time Frame: From baseline until 12 months after the treatment ]
    ESR (eerythrocyte sedimentation rate) level with mm/h as unit of measure
  • Change in IgG level [ Time Frame: From baseline until 12 months after the treatment ]
    IgG (immunoglobin G) level with g/L as unit of measure
  • Change in MCD-related overall symptom score [ Time Frame: From baseline until 12 months after the treatment ]
    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) [ Time Frame: 12 months after the last patient begins study treatment. ]
    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) [ Time Frame: 12 months after the last patient begins study treatment ]
    Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BCD Regimen in Newly Diagnosed Idiopathic Multicentric Castleman's Disease (iMCD)
Official Title  ICMJE Bortezomib, Cyclophosphamide and Dexamethasone (BCD) in Newly Diagnosed Idiopathic Multicentric Castleman's Disease (iMCD) : a Prospective, Single-center, Single-arm, Phase-II Pilot Trial
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This will be a single center, single arm, phase-II pilot study.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Idiopathic Multicentric Castleman's Disease
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: BCD regimen
Bortezomib, cyclophosphamide and dexamethasone (the BCD regimen) would be utilized in newly diagnosed iMCD (idiopathic Multicentric Castleman's disease) patients
Interventions:
  • Drug: Bortezomib
  • Drug: Cyclophosphamide
  • Drug: Dexamethason
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 9, 2019) 		30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2023
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03982771
Other Study ID Numbers  ICMJE ZS-1892
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jian Li, Peking Union Medical College Hospital
Study Sponsor  ICMJE Peking Union Medical College Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Peking Union Medical College Hospital
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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