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

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
1.1 Primary Objective: 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: 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.

Official Title
-----------------
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

Conditions
-----------------
Lymphoma, Non Hodgkin's Lymphoma

Intervention / Treatment
-----------------
* Drug: Cyclophosphamide, Doxorubicin, Vincristine and Prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cyclophosphamide, Doxorubicin, Vincristine and Prednisone|Rituximab will be administered on day 1 of courses 1-6 at 375 mg/m2 concurrently with CHOP-R.All patients will receive antiemetics priorchemotherapy.Courses will be repeated every 14 days.If blood counts don't allow re-treatment on day 14 the counts will be repeated at least twice per week until recovery allows re-treatment.The aim is to achieve a dose that will be as close as possible to 250 mcg and that will result in grade 0 or grade 1A or 1B toxicity at the most. The dose of PEG-Filgrastim will initially be fixed at 3 mg until dose level +3 is reached (which includes 250 mcg Leukine) at which time the dose of Neulasta will be escalated if necessary. All patients will receive Neulasta as a subcutaneous injection on the day 3.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I-II Study of Dose Dense of PEG-Filgrastim and GM-CSF combined with CHOP-R |  | up to 3 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aggressive Non-Hodgkin's Lymphoma