RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known if giving radiation therapy after stem cell transplantation is more effective than stem cell transplantation alone in treating relapsed or refractory non-Hodgkin's lymphoma. PURPOSE: Randomized phase III trial to determine the effectiveness of radiation therapy in treating patients who have relapsed or refractory non-Hodgkin's lymphoma and have undergone autologous stem cell transplantation.

Condition	Treatment or Intervention	Phase
recurrent adult diffuse small noncleaved cell/Burkitt's lymphoma recurrent adult T-cell leukemia/lymphoma recurrent adult diffuse large cell lymphoma anaplastic large cell lymphoma Waldenstrom's Macroglobulinemia	Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the 3-year progression-free survival in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma treated with high-dose chemotherapy and autologous hematopoietic stem cell transplantation with or without involved-field radiotherapy. II. Compare the overall survival in patients treated with these regimens. III. Compare 3-year progression-free disease within and outside radiotherapy fields in patients treated with these regimens. IV. Compare quality of life in patients treated with these regimens. V. Compare the toxic effects of these regimens in these patients .

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to response to pre-salvage chemotherapy (primary refractory disease vs relapse), response to post-salvage chemotherapy (complete/unconfirmed complete vs partial), and participating center. Within 6-8 weeks after completion of autologous hematopoietic stem cell transplantation, patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo involved-field radiotherapy (IFRT) 5 days a week for 3-5 weeks in the absence of unacceptable toxicity. Arm II: Patients undergo observation only. Quality of life in arm I is assessed at baseline, on day 1 of IFRT, at weeks 2 and 4 during IFRT, at 1 month, 4 months, every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years. Quality of life in arm II is assessed at baseline, 1 month, 2 months, every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years. Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this study within 4.2 years.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed non-Hodgkin's lymphoma

• Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell lymphoma and T-cell rich B-cell lymphoma)
• Previous indolent lymphoma (follicular center cell lymphoma, marginal zone lymphoma, including extranodal MALT lymphoma and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse
• Peripheral T-cell lymphoma
• Anaplastic large cell lymphoma (T cell or null cell)
• Small non-cleaved Burkitt-like lymphoma

Relapsed or refractory disease after first-line anthracycline-based chemotherapy

• Bulky disease, nodal or extranodal (Clinically or radiographically measurable mass at least 5 cm in diameter) OR
• Non-bulky disease, nodal or extranodal, excluding diffuse organ (lung, liver, kidney, or bone marrow) involvement (Clinically or radiographically measurable disease more than 1.5 cm in greatest transverse diameter)

Biopsy at relapse not required except for transformed lymphomas

• Patients with transformed lymphoma at diagnosis, but with indolent histology without transformation at relapse, are not eligible

No patients with stage IA or IIA disease at initial diagnosis who, at time of relapse or diagnosis of refractory disease prior to salvage, remained in stage IA or IIA, with no new disease sites, without having received radiotherapy

Received up to 2 regimens and 4 courses of salvage chemotherapy

• Monoclonal antibodies (e.g., rituximab) are not considered salvage chemotherapy
• Achieved complete response (CR), unconfirmed CR, or partial response (PR) if bulky disease

OR

• Achieved PR (but not CR) if non-bulky disease

No residual disease involving extranodal organs diffusely (e.g., liver, lung, bone, kidney, or leptomeningeal) after salvage chemotherapy

Planned autologous hematopoietic stem cell transplantation (ASCT)

• ASCT conditioning must be with high-dose BEAM (carmustine, etoposide, cytarabine, and melphalan) chemotherapy

No disease progression after ASCT

No major organ complication or poor hematologic recovery from ASCT that would preclude initiation of study radiotherapy within 14 weeks after ASCT

No more than 2 non-contiguous nodal or extranodal areas of bulky/residual disease requiring more than 2 separate involved-field radiotherapy volume arrangements (e.g., field arrangement covering up to 2 involved lymph node regions or extranodal sites, with or without 1 adjacent nodal/region or extranodal site)

No active CNS lymphoma (parenchymal brain and/or leptomeningeal)

--Prior/Concurrent Therapy--

Biologic therapy:

• See Disease Characteristics
• No prior radioimmunotherapy

Chemotherapy: See Disease Characteristics

Endocrine therapy: Not specified

Radiotherapy:

• See Disease Characteristics
• No prior total body irradiation
• No prior radiotherapy to the site of bulky disease or residual tumor

Surgery: Not specified

Other:

• No other concurrent anti-cancer therapy unless documentation of disease progression

--Patient Characteristics--

Age: 18 and over

Performance status: ECOG 0-2

Life expectancy: Not specified

Hematopoietic: See Disease Characteristics

Hepatic: Not specified

Renal: Not specified

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except basal cell carcinoma of the skin

Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada
Canada, Ontario
      Cancer Care Ontario-Hamilton Regional Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada
      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada
Canada, Quebec
      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada

Study chairs or principal investigators

Richard Tsang,  Study Chair,  National Cancer Institute of Canada   

Study ID Numbers:  CDR0000069214; CAN-NCIC-LY8
Record last reviewed:  June 2003
Last Updated:  October 13, 2004
Record first received:  March 8, 2002
ClinicalTrials.gov Identifier:  NCT00031668
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08