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

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

Detailed Description
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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.

Official Title
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Thalidomide, Cyclophosphamide and Prednisone in Newly Diagnosed Multicentric Castleman's Disease: a Prospective, Single-center, Single-arm, Phase-II Pilot Trial

Conditions
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Multicentric Castleman Disease

Intervention / Treatment
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* Drug: Thalidomide, cyclophosphamide and prednisone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This will be a single center, single arm, phase-II pilot study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCP regimen<br>Thalidomide, cyclophosphamide and prednisone （TCP regimen）would be used for newly-diagnosed symptomatic MCD patients | Drug: Thalidomide, cyclophosphamide and prednisone<br>* 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.<br>* Other names: TCP regimen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Durable Tumor and Symptomatic Response | 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. | From baseline to the time point when a patient achieves treatment response for 24 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | 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. | 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 | 
| Overall Survival | Overall survival, defined as the time to patients' death, is measured. | From date of randomization until the date of death from any cause, assessed up to 36 months. | 
| Change in SF-36 Score | 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. | From baseline to 24 weeks after 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) | 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 ( ≥3 Grade) | Number of participants with treatment-related serious adverse events as assessed by CTCAE v4.0 (patients with grades ≥3 would be included) | From initiation of TCP regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efficacy, Multicentric Castleman's Disease, Thalidomide, cyclophosphamide and prednisone (TCP regimen), Safety