Chemotherapy and Radiation Therapy Plus Bone Marrow Transplantation in Treating Patients With Aggressive Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. PURPOSE: Randomized phase III trial to study the effectiveness of chemotherapy and radiation therapy plus bone marrow transplantation in treating patients who have aggressive non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Assess the rate of remission in patients with aggressive non-Hodgkin's lymphoma treated with high-dose chemotherapy and radiotherapy plus autologous bone marrow transplantation. Determine the efficacy and toxic effects of this regimen in these patients. OUTLINE: This is a randomized, placebo-controlled, multicenter study. Patients are stratified according to risk group (good vs intermediate vs poor). Patients undergo harvest of autologous bone marrow stem cells after priming chemotherapy and before transplantation. Patients receive induction chemotherapy comprising the CHOP or VAPEC-B regimen. The CHOP regimen consists of vincristine (VCR) IV, cyclophosphamide (CTX) IV, and doxorubicin (DOX) IV on day 1 and oral prednisolone (PRDL) on days 1-5. Treatment repeats every 3 weeks for six courses. The VAPEC-B regimen consists of DOX IV on days 1, 15, 29, 43, 57, and 71; CTX IV on days 1, 29, and 57; VCR IV on days 8, 22, 36, 50, and 64; bleomycin IV on days 8, 36, 64; oral etoposide (VP-16) on days 15-19, 43-47, and 71-75; and oral PRDL daily for 13 weeks. Patients then may undergo radiotherapy for 2-3 weeks to areas of original bulk or residual disease. Good-risk group: Patients are randomized to one of two treatment arms. Arm I: Patients receive no further treatment. Arm II: Patients receive melphalan (L-PAM) before or after total body irradiation (TBI), which is delivered in 3 fractions over 24 hours. After completion of radiotherapy, patients undergo autologous bone marrow transplantation (AuBMT). Intermediate- or poor-risk group: Patients are randomized one of three treatment arms. Arm III: Patients receive L-PAM IV on day -2 and AuBMT on day 0. Arm IV: Patients receive treatment as in arm II. Arm V: Patients receive carmustine IV on day -6, VP-16 IV once daily and cytarabine IV twice daily on days -5 to -2, and L-PAM IV on day -1. Radiotherapy to bulk disease begins after completion of chemotherapy. Patients undergo AuBMT on day 0. Patients are followed monthly for 3 months, every 2 months for 1 year, every 4 months for 2 years, and then every 6 months thereafter. PROJECTED ACCRUAL: Not specified

Official Title
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A Randomised Study of High Dose Chemotherapy/Radiotherapy and Autologous Bone Marrow Transplantation in Patients With High Grade Malignant Non-Hodgkin's Lymphoma (Kiel Classification) According to Prognostic Groups

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: bleomycin sulfate
* Drug: carmustine
* Drug: cyclophosphamide
* Drug: cytarabine
* Drug: doxorubicin hydrochloride
* Drug: etoposide
* Drug: melphalan
* Drug: prednisolone
* Drug: vincristine sulfate
* Procedure: autologous bone marrow transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed aggressive non-Hodgkin's lymphoma requiring chemotherapy Stage II, III, or IV B cell: Centroblastic Immunoblastic Large cell anaplastic Non-Burkitt lymphoblastic T cell: Pleomorphic medium cell Pleomorphic large cell Immunoblastic Large cell anaplastic Lymphoblastic No Burkitt (L3) subtype No large mediastinal mass OR Stage I, II, III, or IV Bulk disease greater than 10 cm Nodal or extranodal site No primary localized gut lymphoma No CNS involvement PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: Not specified Life expectancy: Not specified Hematopoietic: No concurrent bone marrow dysplastic syndromes Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) Renal: Creatinine no greater than 2.5 times ULN Other: No other malignancy except skin cancer or stage I cervical cancer Not pregnant PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 65 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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bleomycin sulfate|nan|
|Drug: carmustine|nan|
|Drug: cyclophosphamide|nan|
|Drug: cytarabine|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: etoposide|nan|
|Drug: melphalan|nan|
|Drug: prednisolone|nan|
|Drug: vincristine sulfate|nan|
|Procedure: autologous bone marrow transplantation|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult diffuse mixed cell lymphoma, stage I adult diffuse large cell lymphoma, stage I adult immunoblastic large cell lymphoma, stage I adult lymphoblastic lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult immunoblastic large cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, contiguous stage II adult lymphoblastic lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult immunoblastic large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult lymphoblastic lymphoma