Trial Information

Autologous Blood or Marrow Transplantation for Aggressive Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning

OBJECTIVES:

Primary

- Determine event-free survival of patients with aggressive non-Hodgkin's lymphoma
treated with early high-dose therapy and autologous peripheral blood stem cell (PBSC)
or bone marrow transplantation (BMT) based on positive fludeoxyglucose F 18 positron
emission tomography (FDG-PET) results obtained during first-line chemotherapy.

- Compare event-free survival of patients treated with this regimen with historical
event-free survival of patients with positive FDG-PET results obtained during
first-line chemotherapy that are not treated with early high-dose therapy.

Secondary

- Compare overall survival of patients treated with a standard treatment regimen vs early
high-dose therapy and autologous PBSC or BMT based on FDG-PET results obtained during
first-line chemotherapy.

- Determine the predictive value of an early negative FDG-PET result in these patients.

- Correlate International Prognostic Index risk category with FDG-PET results and overall
outcome in these patients.

OUTLINE: This is a pilot study.

- First-line chemotherapy: Patients receive cyclophosphamide IV, doxorubicin IV, and
vincristine IV on day 1, oral prednisone on days 1-5, and rituximab IV on day 1
(patients with CD20-positive disease only) OR another standard first-line chemotherapy
regimen. Treatment repeats every 14-21 days for 2 or 3 courses in the absence of
disease progression or unacceptable toxicity.

- Radiographic staging: Between days 11-20 of course 2 or 3 OR days 11-13 of course 3 of
first-line chemotherapy, patients receive fludeoxyglucose F 18 (FDG) IV. One hour
later, patients undergo whole-body FDG-positron emission tomography (PET) and CT scan.
Patients with no evidence of malignant disease by FDG-PET (i.e., negative result)
receive a standard treatment regimen that may include localized radiotherapy for
limited stage or bulky disease followed, 4-6 weeks later, by a repeat whole-body
FDG-PET and CT scan. Patients with progressive disease after first-line chemotherapy
are removed from the study. Patients with evidence of malignant disease by FDG-PET
(i.e., positive result) and stable disease or better proceed to ESHAP chemotherapy.

- ESHAP chemotherapy: Patients receive etoposide IV over 2 hours, methylprednisolone IV,
and cisplatin IV over 3 hours on days 1-4 followed by cytarabine IV over 2 hours on day
5. Patients with CD20-positive disease also receive rituximab IV on day 1. Treatment
repeats every 14-21 days for 2 courses in the absence of disease progression or
unacceptable toxicity. Beginning 1 day after completion of course 2, patients receive
filgrastim (G-CSF) subcutaneously once daily followed by leukapheresis to collect
peripheral blood stem cells (PBSC). Some patients may also undergo bone marrow (BM)
harvest if sufficient PBSC are not collected. Patients with a sufficient number of stem
cells proceed to high-dose therapy and autologous PBSC transplantation (PBSCT) or BM
transplantation (BMT).

- High-dose therapy and PBSCT or BMT: No more than 4 weeks after completion of PBSC
collection or BM harvest, patients receive high-dose therapy that may include
cyclophosphamide and total-body irradiation OR busulfan and cyclophosphamide. Patients
then undergo PBSCT or BMT. Between 4-6 weeks after completion of PBSCT or BMT, patients
undergo repeat whole-body FDG-PET and CT scan. Patients may also undergo consolidative
radiotherapy to the sites of bulky disease at the discretion of the physician.

After completion of study treatment, patients are followed at 4 weeks, every 3 months for 2
years, every 6 months for 1 year, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 18 months.