Trial Information

Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma

OBJECTIVES:

- Determine the complete remission rate in patients with low-intermediate-,
high-intermediate-, or high-risk, CD20-positive, diffuse large B-cell lymphoma treated
with induction chemotherapy and rituximab followed by consolidation chemotherapy with
or without rituximab, total body irradiation, and autologous peripheral blood stem cell
transplantation.

- Evaluate positron emission tomography imaging for risk stratification of aggressive
lymphoma by biopsy confirmation of residual lesions at interim restaging in patients
treated with these regimens.

- Determine the safety and toxicity of these regimens in these patients.

OUTLINE: Patients are stratified according to risk (low-intermediate vs high-intermediate or
high).

Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV over
15 minutes, and vincristine IV over 1-2 minutes on day 1; oral prednisone once daily on days
1-5; and filgrastim (G-CSF) subcutaneously (SC) once daily on days 7-11 or PEG-filgrastim
once at least 24 hours after infusion. Patients also receive rituximab IV 2-3 days apart for
a total of 2 doses during the week prior to the first course of chemotherapy and on day 1 of
courses 2-4 of chemotherapy. Treatment repeats every 14 days for a total of 4 courses in the
absence of disease progression or unacceptable toxicity.

After the completion of induction chemotherapy, patients undergo CT scan and positron
emission tomography (PET) scanning. If the PET scan is positive in one or more nodal sites,
a repeat biopsy is performed. Patients with a negative PET scan OR a negative repeat biopsy
(including no evidence of lymphoma on repeat bone marrow biopsy) are assigned to receive
regimen A for consolidation therapy. Patients with a positive repeat biopsy are assigned to
receive regimen B for consolidation therapy.

- Regimen A: Patients receive consolidation chemotherapy comprising etoposide IV over 1
hour on days 1-3, ifosfamide IV continuously over 24 hours on day 2, carboplatin IV on
day 2, and G-CSF SC once daily on days 5-12 or PEG-filgrastim once at least 24 hours
after infusion. Treatment repeats every 14 days for a total of 3 courses in the absence
of disease progression or unacceptable toxicity.

- Regimen B: Patients receive consolidation chemotherapy as in regimen A for 3 courses.
Patients also receive rituximab IV on days -3 to -1 of course 3 of chemotherapy.
Patients undergo leukapheresis at the completion of course 3 (G-CSF continues from day
5 until the end of leukapheresis). After completion of leukapheresis, patients begin a
regimen of high-dose chemoradiotherapy comprising either total body irradiation twice
daily on days -10 to -7 and ifosfamide IV over 1 hour and etoposide IV continuously on
days -6 to -2 or BEAM chemotherapy comprising carmustine, etoposide, cytarabine, and
melphalan. Autologous peripheral blood stem cells (APBSC) are reinfused on day 0.
Patients also receive G-CSF SC daily beginning on day 5 and continuing until blood
counts recover. Beginning on day 42 post-APBSC, if blood counts have recovered,
patients receive rituximab IV once weekly for 4 weeks. Rituximab is repeated beginning
on day 180 in the absence of disease progression.

Patients who receive consolidation therapy on regimen A are followed at 4-6 weeks after
chemotherapy and patients who receive consolidation therapy on regimen B are followed at
90-120 days after transplantation. All patients are followed closely for 5 years and then
annually thereafter.

PROJECTED ACCRUAL: A total of 40-98 patients will be accrued for this study within 4 years.