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