S0410 Tandem Stem Cell Transplantation in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

OBJECTIVES:

• Determine the 2-year progression-free survival of patients with progressive or recurrent Hodgkin's lymphoma treated with tandem autologous stem cell transplantation (2 courses of high-dose therapy with autologous stem cell rescue).
• Determine the response rate in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy. No more than 6 weeks later, patients proceed to autologous hematopoietic stem cell collection.
• Autologous hematopoietic stem cell collection: Patients undergo autologous hematopoietic stem cell collection. Patients with an inadequate number of collected stem cells are removed from the study.
• Pre-transplant salvage radiation: Patients with residual tumor greater than 5 cm after initial salvage therapy undergo involved-field radiotherapy. All patients then proceed to the first preparative regimen.
• First preparative regimen: Patients receive high-dose melphalan IV on day -1.
• First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. At least 28 days later, patients proceed to second preparative regimen.
• Second preparative regimen: Patients receive 1 of the following preparative regimens:

• Total-body irradiation (TBI)-based regimen: Patients undergo TBI twice daily on days -8 to -5. Patients also receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 1 hour on day -2.
• Carmustine-based regimen: Patients receive carmustine IV over 2 hours on days -6 to -4, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2.
• Second autologous SCT: Patients undergo second autologous SCT on day 0. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 7 years.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study over 2 years.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed Hodgkin's lymphoma

• Relapsed or refractory disease
• Biopsy or radiological evidence of disease at time of recurrence/progression required
• Has received ≥ 1 prior systemic chemotherapy regimen
• No clonal abnormalities in marrow collection
• Must undergo involved-field radiotherapy if bulky disease > 5 cm
• Must have adequate sections of original diagnostic specimen available for review

• Needle aspirations or cytologies are not adequate
• No prior lymphoma, myelodysplastic syndromes, or leukemia (even if disease free > 5 years)
• Patients who relapse after achieving a complete remission must complete a minimum of 2 courses of salvage chemotherapy or radiation therapy to determine if sensitive or resistant recurrent disease is present
• No central nervous system (CNS) involvement

PATIENT CHARACTERISTICS:

Age

• 15 to 70

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Hodgkin's disease)

Renal

• Creatinine clearance ≥ 60 mL/min
• Creatinine ≤ 2 times upper limit of normal

Cardiovascular

• None of the following conditions requiring therapy:

• Coronary artery disease
• Cardiomyopathy
• Congestive heart failure
• Arrhythmias
• Ejection fraction ≥ 45% by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram

Pulmonary

• Adequate pulmonary function
• Corrected diffusing capacity of lung for carbon monoxide (DLCO) ≥ 60% OR
• Forced Expiratory Volume in One Side (FEV_1) ≥ 60% of predicted

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• No known HIV or AIDS infection
• No active bacterial, fungal, or viral infection
• No medical condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• Not specified