High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease
High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill tumor cells.
PURPOSE: Phase II trial to study the effectiveness of chemotherapy plus radiation therapy in treating patients with refractory or relapsed Hodgkin's lymphoma.
OBJECTIVES:
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).
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.
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.
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:
PATIENT CHARACTERISTICS:
Age:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Pulmonary:
Other:
No uncontrolled infection
HIV negative
At least 5 years since prior malignancy except:
Not pregnant or nursing
Fertile women must use effective contraception
PRIOR CONCURRENT THERAPY: