High Dose Sequential Therapy for Poor Risk Recurrent or Refractory Hodgkin's Disease
- To evaluate the feasibility and toxicity of high-dose sequential therapy comprising
high-dose etoposide and cyclophosphamide with filgrastim (G-CSF) support followed by 2
courses of high-dose therapy and autologous stem cell transplantation in patients with
poor-risk recurrent or refractory Hodgkin lymphoma.
- To analyze the response rate, progression-free survival, and overall survival of
patients treated with this regimen.
- To determine the percentage of patients who can achieve a minimal disease status after
two courses of Hodgkin lymphoma chemotherapy and before "classical autologous stem cell
- First high-dose chemotherapy*: Patients receive high-dose cyclophosphamide IV over 2
hours followed by etoposide IV over 4 hours.
NOTE: *Patients with minimal disease (i.e., a single lymph node ≤ 2 cm in maximal horizontal
diameter or a > 75% reduction in a bulky (≥ 10 cm) tumor mass AND no morphological evidence
of active bone marrow disease) at initial evaluation do not receive the first high-dose
chemotherapy but proceed directly to peripheral blood stem cell (PBSC) mobilization with
filgrastim (G-CSF) for 3 days and PBSC collection beginning on day 4.
- Peripheral stem cell mobilization and collection: Patients receive G-CSF subcutaneously
beginning 96 hours after completion of etoposide and continuing through completion of
PBSC collection. Patients undergo leukapheresis to collect PBSC for reinfusion after
additional high-dose therapy.
- Second high-dose chemotherapy: Patients receive high-dose melphalan IV over 30 minutes
on day -1.
- First PBSC infusion: At least 24 hours after completion of melphalan, patients undergo
reinfusion of PBSC on day 0.
- Local radiotherapy: Patients with a localized tumor mass > 5 cm after the second course
of chemotherapy or a previous history of bulky disease (> 10 cm or mediastinal mass >
1/3 of transverse thoracic diameter) that has not been irradiated may receive local
radiotherapy for 2 weeks, at the discretion of the principal investigator.
- High-dose therapy: Eight to 12 weeks after completion of the second course of
chemotherapy, patients receive 1 of 2 regimens.
- Regimen A: Patients undergo fractionated total body irradiation 3 times daily on
days -8 to -5 (10 fractions) and receive high-dose etoposide IV over 4 hours on
day -4 and cyclophosphamide IV on day -2.
- Regimen B: Patients receive high-dose carmustine IV over 4 hours on days -7 to -5
and etoposide and cyclophosphamide as in regimen A.
- Second PBSC infusion: At least 48 hours after completion of cyclophosphamide, patients
undergo reinfusion of PBSC on day 0.
After completion of study therapy, patients are followed at day 60 and then every 3 months
for up to 1 year.
Primary Purpose: Treatment
Eileen P. Smith, MD
Beckman Research Institute
United States: Federal Government