Rituximab and Combination Chemotherapy With or Without Bleomycin Sulfate in Treating Patients With Primary Mediastinal Large B-Cell Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabBiological: bleomycin sulfateDrug: EPOCH regimen
- Registration Number
- NCT00983944
- Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating large B-cell lymphoma.
PURPOSE: This randomized phase II trial is studying how well rituximab and combination chemotherapy work when given with or without bleomycin sulfate in treating patients with primary mediastinal large B-cell lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* To determine the complete response rate based on PET/CT scan criteria in patients with primary mediastinal large B-cell lymphoma (PMLCL) treated with dose-adjusted rituximab, etoposide, doxorubicin hydrochloride, vincristine sulfate, cyclophosphamide, and prednisone with or without bleomycin sulfate.
Secondary
* To characterize the progression-free survival (PFS) of patients treated with these regimens.
* To assess the toxicity profiles associated with these regimens in these patients.
* To determine the prognostic significance of a mid-therapy PET scan and an end-of-therapy PET scan in achieving complete response and in predicting 2-year PFS of patients treated with these regimens.
* To explore the effect of involved-field radiotherapy on 2-year PFS of patients who are PET positive at the end of chemotherapy.
* To explore the efficacy of an end-of-therapy PET/CT scan in predicting which patients can avoid radiotherapy.
* To characterize the overall survival of patients treated with these regimens.
* To prospectively validate a pattern of immunohistochemical staining, including nuclear c-REL, TRAF-1, c-JUN, and Gal1, to accurately distinguish PMLCL from other lymphoid malignancies.
* To determine if levels of soluble CD30 correlate with disease activity in PMLCL.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
* Arm I (EPOCH-R): Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II (R-VACOP-B): Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10.
In both arms, patients undergo PET/CT scans at baseline, mid-therapy, and after completion of chemotherapy. Patients with stable or progressive disease after completion of chemotherapy are removed from the study. Patients with complete response undergo observation. Patients with partial response undergo involved-field radiotherapy to any area of bulky disease at diagnosis and to any FDG-avid area on PET scan 3-4 weeks after completion of chemotherapy. These patients then undergo additional PET/CT scan at 8-10 weeks after completion of radiotherapy.
Blood samples are collected at baseline, during mid-therapy restaging, and after completion of chemotherapy for analysis of soluble CD30 levels by ELISA. Previously collected tissue samples are obtained for biomarker analysis by IHC.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I (EPOCH-R) vincristine sulfate Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm I (EPOCH-R) rituximab Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm I (EPOCH-R) EPOCH regimen Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm II (R-VACOP-B) bleomycin sulfate Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm II (R-VACOP-B) rituximab Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm II (R-VACOP-B) EPOCH regimen Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm II (R-VACOP-B) vincristine sulfate Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm I (EPOCH-R) etoposide Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm I (EPOCH-R) cyclophosphamide Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm I (EPOCH-R) doxorubicin hydrochloride Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm I (EPOCH-R) prednisone Patients receive rituximab IV on day 1; etoposide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 30 minutes on day 5; and oral prednisone twice daily on days 1-5. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm II (R-VACOP-B) cyclophosphamide Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm II (R-VACOP-B) doxorubicin hydrochloride Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm II (R-VACOP-B) etoposide Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10. Arm II (R-VACOP-B) prednisone Patients receive rituximab IV and doxorubicin hydrochloride IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; cyclophosphamide IV over 30 minutes on day 1 of weeks 1, 5, and 9; etoposide IV over 1 hour on day 1 and then orally on days 2 and 3 of weeks 3, 7, and 11; bleomycin sulfate IV and vincristine sulfate IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; and oral prednisone on days 1-7 of week 1 and then every other day in weeks 2-10.
- Primary Outcome Measures
Name Time Method Complete response rate Up to a year
- Secondary Outcome Measures
Name Time Method Overall survival Up to 3 years Correlation of soluble CD30 levels with disease activity in PMLCL Up to a year Two-year progression-free survival Up to 2 years Toxicity as assessed by NCI CTCAE v3.0 Up to 3 years Immunohistochemical staining results Up to a year