Chemotherapy Plus Radiation Therapy in Treating Patients With Refractory or Relapsed Hodgkin's Lymphoma

OBJECTIVES:

• Assess the efficacy of a high-dose chemoradiotherapy regimen in patients with refractory or relapsed Hodgkin's lymphoma.

OUTLINE: Patients are stratified into 1 of 3 treatment arms (0-1 adverse prognostic factors vs 2 adverse prognostic factors vs 3 adverse prognostic factors).

• Arm I (0-1 adverse prognostic factors): Patients receive ifosfamide by 24 hour infusion on day 2. Carboplatin is administered on day 2. Etoposide IV is administered once daily on days 1-3. Patients then receive filgrastim (G-CSF) subcutaneously or IV on days 5-12. Patients receive another course of ICE chemotherapy 2-3 weeks after the first course.

Leukapheresis is performed once WBC reaches at least 3000/mm^3 and continues until enough peripheral blood stem cells are collected.

Patients who have never received prior radiotherapy will receive accelerated hyperfractionated total lymphoid irradiation (TLI) twice a day for 5 days (days -10 to -6). Cyclophosphamide IV is then administered on days -5 and 4. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2).

Patients who have had prior radiotherapy receive high dose chemotherapy. Cyclophosphamide IV is administered on days -6 and -5. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2.

Peripheral blood stem cells are infused 24-36 hours after high-dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

• Arm II (2 adverse prognostic factors): Patients receive the first course of ICE as in Arm I.

Apheresis is performed once WBC is greater than 3000/mm^3 and continues until enough cells are collected. The second course of ICE is then administered.

Ifosfamide is administered by 48 hour continuous infusion on days 1-2. Carboplatin is administered on day 3. Etoposide IV is administered every 12 hours for 3 doses beginning on day 1. Patients receive G-CSF on days 5-14.

Patients who have never received prior radiotherapy will receive accelerated hyperfractionated TLI for 5 days (days -10 to -6). Cyclophosphamide IV is then administered every 12 hours on days -5 to -2. Etoposide IV is administered by continuous infusion over 4 days (days -5 to -2).

Patients who have had prior radiotherapy receive high-dose chemotherapy. Cyclophosphamide IV is administered every 12 hours on days -6 to -3. Etoposide IV is administered by continuous infusion over 4 days (days -6 to -3). Carmustine IV is administered on day -2.

Peripheral blood stem cells are infused 24-36 hours after high dose chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

• Arm III (3 adverse prognostic factors): Patients receive cyclophosphamide IV daily for 2 days, then G-CSF beginning on day 4 until blood stem cells are collected.

Patients then undergo apheresis until enough cells are collected.

Patients receive high-dose chemotherapy. Ifosfamide IV is administered for 1 hour. Etoposide is administered by continuous infusion for 12 hours. Carboplatin IV is administered for 1 hour. Etoposide is again administered by continuous infusion for 12 hours. Treatment is repeated daily for 5 days.

Peripheral blood stem cells are reinfused 24-36 hours after the last dose of chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

Patients who have never received prior radiation will now receive accelerated hyperfractionated TLI twice daily for 5 days. Patients receive a second course of high dose chemotherapy 45-90 days after reinfusion of cells. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2.

Patients who have received prior radiation therapy receive a second course of high-dose chemotherapy. Carmustine IV is administered on day -7. Etoposide IV and cytarabine IV are administered every 12 hours for 4 days (days -6 to -3). Melphalan IV is administered on day -2.

Peripheral blood stem cells are reinfused 24-48 hours after completion of second course chemotherapy. G-CSF is administered beginning on day 1 and continuing until blood counts recover.

Patients are followed every 3 months for the first 2 years, every 4 months during years 3-5, and every 6 months thereafter.

PROJECTED ACCRUAL: This study will accrue 80 patients within 4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed residual or relapsed Hodgkin's lymphoma following conventional dose standard chemotherapy
• Presence of the following prognostic factors are allowed:

• B symptoms (fever, weight loss, night sweats)
• Extranodal disease
• Complete remission of less than 1 year duration

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2.0 mg/dL unless history of Gilbert's disease
• No chronic active or persistent hepatitis

Renal:

• No history of chronic renal insufficiency
• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No myocardial infarction within the past 6 months
• No unstable angina
• No significant cardiac arrhythmias other than chronic atrial fibrillation
• Ejection fraction at least 50%

Pulmonary:

• DLCO at least 50%

Other:

• No uncontrolled infection
• HIV negative
• At least 5 years since prior malignancy except:

• Curatively treated cutaneous basal cell carcinoma
• Carcinoma in situ of the cervix
• Not pregnant or nursing
• Fertile women must use effective contraception

PRIOR CONCURRENT THERAPY:

• Must have failed conventional dose standard chemotherapy