Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, Rituximab Pateinets With Aggresive NHL

Protocol CCAM 05-02 " Phase I-II Study of Dose Dense of PEG Filgrastim and GM-CSF as Support for Dose Desnse CHOP-R Front Line Therapy for Aggressive Non Hodgkin's Lymphoma"

We now propose to investigate the combination of CHOP-Rituxan plus PEG-Filgrastim (PEG-filgrastim) and GM-CSF. PEG-Filgrastim would be given in order to allow us to administer the chemotherapy courses every 2 weeks with the practical advantage of requiring only one dose of PEG-filgrastim instead of daily doses of G-CSF.

1.1 Primary Objective:

1. To identify the ideal dose of the combination of CHOP-R with PEG-Filgrastim (Neulasta) using first a fixed dose of Neulasta and an escalating dose of GM-CSF (Leukine) up to 250 mcg. When that dose is reached, if possible, the dose of Neulasta will be increased stepwise. CHOP-R will be delivered every 14 days at a fixed standard dose with dose adjustments of PEG-Filgrastim and GM-CSF upwards and downwards according to nadir or zenith blood counts.

   1.2 Secondary Objective:

2. To generate preliminary pilot data as to the effectiveness of the regimen in inducing very early remissions as measured by the CT-PET scan technique.

Inclusion Criteria:

• Patients with previously untreated aggressive non-Hodgkin's Lymphoma. Aggressive histologies include follicular large cell, diffuse large cell, peripheral T cell, transformed lymphomas, Lymphoblastic lymphomas, Burkitt and Burkitt like lymphomas.
• Must have measurable or evaluable disease.
• Stage I-IV patients are eligible
• Patients must be 18 years or older.
• No evidence of grade 3 or more neurosensory or neuromotor dysfunction (see appendix- toxicity criteria)
• Written Consent

Exclusion Criteria:

• HIV positive patients and those with Hepatitis B or C will be excluded from this protocol.
• Patients with inadequate bone marrow and organ function as defined below:
• Neutrophils <1,000/l
• Platelets <100,000/l
• Billirubin >2
• Creatinine >2.0 or estimated CrCl <30 cc/min
• CNS involvement by Lymphoma.
• Uncontrolled intercurrent disease including arrhythmias, angina pectoris, Class III-IV Congestive heart failure (CHF symptoms on less than ordinary exertion or at rest) or active infection.
• Active infection or fever > 38.2 degrees C unless due to lymphoma.
• Subject is not using adequate contraceptive precautions.
• Pregnancy or breast feeding