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出境医 / 临床实验 / TCP Regimen in Newly Diagnosed MCD:a Prospective, Single-center, Single-arm, Phase-II Pilot Trial

TCP Regimen in Newly Diagnosed MCD:a Prospective, Single-center, Single-arm, Phase-II Pilot Trial

Study Description
Brief Summary:
To explore the effectiveness and safety of thalidomide, cyclophosphamide and prednisone (TCP regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.

Condition or disease Intervention/treatment Phase
Multicentric Castleman Disease Drug: Thalidomide, cyclophosphamide and prednisone Phase 2

Detailed Description:
This is a single center, open-labeled , single arm, phase-II pilot study which aims to evaluate the efficacy and safety of thalidomide, cyclophosphamide and prednisone (TCP regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.There would be two phases of the study. The treatment and the response evaluation phase will last from the time of enrollment up to 24 months (evaluation will be carried out every 3 months). The follow-up phase to assess for progression of disease will last from 24 months (2 years) to 4 years 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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 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)
Masking Description: open-labeled
Primary Purpose: Treatment
Official Title: Thalidomide, Cyclophosphamide and Prednisone in Newly Diagnosed Multicentric Castleman's Disease: a Prospective, Single-center, Single-arm, Phase-II Pilot Trial
Actual Study Start Date : January 1, 2017
Actual Primary Completion Date : January 1, 2020
Estimated Study Completion Date : January 1, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: TCP regimen
Thalidomide, cyclophosphamide and prednisone （TCP regimen）would be used for newly-diagnosed symptomatic MCD patients
 Drug: Thalidomide, cyclophosphamide and prednisone
  • Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;
  • Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;
  • Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.
Other Name: TCP regimen
Outcome Measures
Primary Outcome Measures :
  1. Number of Patients With Durable Tumor and Symptomatic Response [ Time Frame: From baseline to the time point when a patient achieves treatment response for 24 weeks. ]
    Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 6 months.


Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Progression-free survival (PFS) is defined as the time to death or treatment failure. Treatment failure is defined as: sustained increase in grade ≥2 disease-related symptoms persisting ≥12 weeks; new disease-related grade ≥3 symptoms; sustained >1 point increase in ECOG-PS persisting for ≥12 weeks; radiological progression; or initiation of another treatment for MCD.

  2. Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 36 months. ]
    Overall survival, defined as the time to patients' death, is measured.

  3. Change in SF-36 Score [ Time Frame: From baseline to 24 weeks after treatment. ]
    SF-36 score is a self-administered scoring system which reflects a patient's general health status. SF-36 contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health. Each dimension ranges from 0 to 100. Higher scores mean better outcome. SF-36 score at baseline was compared with SF-36 score at 24 weeks.

  4. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade) [ Time Frame: From initiation of TCP 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 (patients with grades ≥1 would be included)

  5. Number of Participants With Treatment-related Serious Adverse Events as Assessed by CTCAE v4.0 ( ≥3 Grade) [ Time Frame: From initiation of TCP 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 serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)


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

  • Inclusion Criteria:

    • ≥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 MCD 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);
    • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2;
    • 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;
    • ECOG (eastern cooperative oncology group) status above 2;
    • 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.
Contacts and Locations

Locations
Layout table for location information
China, Beijing
Peking Union Medical College Hospital
Beijing, Beijing, China, 100005
Sponsors and Collaborators
Peking Union Medical College Hospital
Tracking Information
First Submitted Date  ICMJE January 31, 2017
First Posted Date  ICMJE February 3, 2017
Results First Submitted Date  ICMJE February 9, 2020
Results First Posted Date  ICMJE April 16, 2020
Last Update Posted Date April 16, 2020
Actual Study Start Date  ICMJE January 1, 2017
Actual Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 5, 2020) 		Number of Patients With Durable Tumor and Symptomatic Response [ Time Frame: From baseline to the time point when a patient achieves treatment response for 24 weeks. ]
Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 6 months.
Original Primary Outcome Measures  ICMJE
 (submitted: February 1, 2017) 		Durable tumor and symptomatic response [ Time Frame: 48 weeks after the last patient begins study treatment. ]
Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman's disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 5, 2020)
  • Progression-free Survival [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months ]
    Progression-free survival (PFS) is defined as the time to death or treatment failure. Treatment failure is defined as: sustained increase in grade ≥2 disease-related symptoms persisting ≥12 weeks; new disease-related grade ≥3 symptoms; sustained >1 point increase in ECOG-PS persisting for ≥12 weeks; radiological progression; or initiation of another treatment for MCD.
  • Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 36 months. ]
    Overall survival, defined as the time to patients' death, is measured.
  • Change in SF-36 Score [ Time Frame: From baseline to 24 weeks after treatment. ]
    SF-36 score is a self-administered scoring system which reflects a patient's general health status. SF-36 contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health. Each dimension ranges from 0 to 100. Higher scores mean better outcome. SF-36 score at baseline was compared with SF-36 score at 24 weeks.
  • Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade) [ Time Frame: From initiation of TCP 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 (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: From initiation of TCP 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 serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2017)
  • Progression-free survival (PFS) [ Time Frame: 48 weeks after the last patient begins study treatment. ]
    defined as the time to tumor PD
  • Overall survival (OS) [ Time Frame: 48 weeks after the last patient begins study treatment. ]
    defined as the time to patients' death
  • Change in SF-36 Score [ Time Frame: From Day 1 of Cycle 1 (baseline) until 48 weeks after the last participant started study treatment ]
    SF-36 score is a self-administered scoring system which contains several aspects and reflects a patient's general health status.
  • Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade) [ Time Frame: 48 weeks 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: 48 weeks 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE TCP Regimen in Newly Diagnosed MCD:a Prospective, Single-center, Single-arm, Phase-II Pilot Trial
Official Title  ICMJE Thalidomide, Cyclophosphamide and Prednisone in Newly Diagnosed Multicentric Castleman's Disease: a Prospective, Single-center, Single-arm, Phase-II Pilot Trial
Brief Summary To explore the effectiveness and safety of thalidomide, cyclophosphamide and prednisone (TCP regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.
Detailed Description This is a single center, open-labeled , single arm, phase-II pilot study which aims to evaluate the efficacy and safety of thalidomide, cyclophosphamide and prednisone (TCP regimen) in newly diagnosed Multicentric Castleman's disease (MCD) patients.There would be two phases of the study. The treatment and the response evaluation phase will last from the time of enrollment up to 24 months (evaluation will be carried out every 3 months). The follow-up phase to assess for progression of disease will last from 24 months (2 years) to 4 years 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)
Masking Description:
open-labeled
Primary Purpose: Treatment
Condition  ICMJE Multicentric Castleman Disease
Intervention  ICMJE Drug: Thalidomide, cyclophosphamide and prednisone
  • Thalidomide: 100mg QN for 1 year; And maintained with 100mg QN for the second year;
  • Cyclophosphamide: 300mg/m2 on Day 1, 8, 15, 22 every month for 1 year;
  • Prednisone: 1mg/kg on Day 1-2, 8-9, 15-16, 22-23 every month for 1 year.
Other Name: TCP regimen
Study Arms  ICMJE Experimental: TCP regimen
Thalidomide, cyclophosphamide and prednisone （TCP regimen）would be used for newly-diagnosed symptomatic MCD patients
Intervention: Drug: Thalidomide, cyclophosphamide and prednisone
Publications * Zhang L, Zhao AL, Duan MH, Li ZY, Cao XX, Feng J, Zhou DB, Zhong DR, Fajgenbaum DC, Li J. Phase 2 study using oral thalidomide-cyclophosphamide-prednisone for idiopathic multicentric Castleman disease. Blood. 2019 Apr 18;133(16):1720-1728. doi: 10.1182/blood-2018-11-884577. Epub 2019 Feb 13.

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 5, 2020) 		25
Original Estimated Enrollment  ICMJE
 (submitted: February 1, 2017) 		55
Estimated Study Completion Date  ICMJE January 1, 2021
Actual Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

  • Inclusion Criteria:

    • ≥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 MCD 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);
    • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2;
    • 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;
    • ECOG (eastern cooperative oncology group) status above 2;
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03043105
Other Study ID Numbers  ICMJE ZS-1159
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 April 2020

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

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