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