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High Dose Sequential Therapy for Poor Risk Recurrent or Refractory Hodgkin's Disease

64 Years
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Trial Information

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.

Inclusion Criteria


- Histologically confirmed Hodgkin lymphoma

- Diagnosis reviewed by the participating institution

- Failed to achieve complete remission (CR) after first-line chemotherapy or
chemoradiotherapy (i.e., induction failure) OR not felt to be curable by radiotherapy

- Relapsed after standard chemotherapy regimen for Hodgkin lymphoma AND has ≥ 1 of the
following poor-risk features:

- Extranodal disease at relapse

- Interval from first CR to relapse < 12 months

- B symptoms at relapse

- Chemo-resistant relapse OR failure to achieve a second CR with conventional
nontransplantation salvage chemotherapy regimen

- No cytogenetic abnormality on cytogenetic analysis of bone marrow


Inclusion criteria:

- SWOG performance status 0-1

- LVEF > 50% by 2D-ECHO or MUGA scan

- Patients with LVEF between 45-50% and without wall motion abnormalities are
assessed on an individual basis after consultation with the cardiologist

- FEV_1 or DLCO > 45% predicted

- Creatinine clearance > 60 mL/min

- HIV-negative

- Hepatitis B surface antigen-negative

- Hepatitis C virus-negative

- ALT ≤ 5 times upper limit of normal

- No inadequate vital organ function

- No active infection

- Fertile patients must use adequate contraception


- See Disease Characteristics

- Concurrent, post-transplantation, consolidative radiotherapy to residual masses
allowed provided the patient has engrafted with a WBC > 4,000/μL and a platelet count
> 100,000/μL

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Eileen P. Smith, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Beckman Research Institute


United States: Federal Government

Study ID:




Start Date:

April 1998

Completion Date:

December 2007

Related Keywords:

  • Lymphoma
  • recurrent adult Hodgkin lymphoma
  • recurrent/refractory childhood Hodgkin lymphoma
  • Hodgkin Disease
  • Lymphoma