Multicentric Castleman Disease
Conditions
Keywords
Multicentric Castleman's Disease, Thalidomide, cyclophosphamide and prednisone (TCP regimen), Efficacy, Safety
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.
Interventions
DRUGThalidomide, 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.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
open-labeled
Intervention model description
This will be a single center, single arm, phase-II pilot study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Durable Tumor and Symptomatic Response | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 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 | 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 | 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) | 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) | 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) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TCP Treatment Group The newly-diagnosed symptomatic MCD patients received thalidomide, cyclophosphamide and prednisone (TCP ) treatment. The accurate dose of TCP regimen is listed as follows.
* 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. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | TCP Treatment Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 40 years |
| Race/Ethnicity, Customized East Asian | 25 Participants |
| Region of Enrollment China | 25 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 25 |
| other Total, other adverse events | 10 / 25 |
| serious Total, serious adverse events | 2 / 25 |
Outcome results
Primary
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.
Time frame: From baseline to the time point when a patient achieves treatment response for 24 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCP Treatment Group | Number of Patients With Durable Tumor and Symptomatic Response | 12 Participants |
Secondary
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.
Time frame: From baseline to 24 weeks after treatment.
Population: Each patient is assessed by SF-36 scoring system, which contains 8 dimensions, including physical functioning, role physical, role emotional, vitality, mental health, social functioning, bodily pain, and general health.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TCP Treatment Group | Change in SF-36 Score | social functioning | 13.6 score on a scale | Standard Deviation 6.7 |
| TCP Treatment Group | Change in SF-36 Score | bodily pain | 15.8 score on a scale | Standard Deviation 6.19 |
| TCP Treatment Group | Change in SF-36 Score | general health | 9.1 score on a scale | Standard Deviation 4.78 |
| TCP Treatment Group | Change in SF-36 Score | physical functioning | 15.1 score on a scale | Standard Deviation 6.78 |
| TCP Treatment Group | Change in SF-36 Score | role physical | 26.7 score on a scale | Standard Deviation 10.53 |
| TCP Treatment Group | Change in SF-36 Score | role emotional | 19.6 score on a scale | Standard Deviation 10.18 |
| TCP Treatment Group | Change in SF-36 Score | vitality | 11.1 score on a scale | Standard Deviation 5.75 |
| TCP Treatment Group | Change in SF-36 Score | mental health | 8.5 score on a scale | Standard Deviation 5.5 |
Secondary
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)
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCP Treatment Group | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 ( ≥1 Grade) | 10 Participants |
Secondary
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)
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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCP Treatment Group | Number of Participants With Treatment-related Serious Adverse Events as Assessed by CTCAE v4.0 ( ≥3 Grade) | 2 Participants |
Secondary
Overall Survival
Overall survival, defined as the time to patients' death, is measured.
Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TCP Treatment Group | Overall Survival | 32.16 months |
Secondary
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.
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| TCP Treatment Group | Progression-free Survival | 23.32 months |