Tailoring Treatment for B Cell Non-hodgkin's Lymphoma Based on PET Scan Results Mid Treatment

The purpose of this study is to assess whether patients who are likely to fail R-CHOP, as predicted by a mid-treatment PET scan, can have an improved outcome if switched to a standard salvage regimen R-ICE (rituximab, ifosfamide, carboplatin, etoposide). Patients who have a negative PET scan after 4 cycles of R-CHOP have an excellent prognosis (\>85% chance of cure) and should complete treatment with 6 cycles of standard R-CHOP. Patients who have a positive PET scan after 4 cycles of R-CHOP have a very poor prognosis (\~10% chance of cure) and may have an improved outcome if switched to a non-cross resistant chemotherapy combination R-ICE.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 18 years of age or older
* newly diagnosed histologically proven CD-20 positive diffuse large B- cell lymphoma by tissue biopsy, listed under peripheral B-cell neoplasm according to the WHO/REAL classification (diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, T-cell rich B-cell lymphoma, intravascular large B-cell lymphoma)
* Advanced stage disease defined as - patients with stage III or stage IV disease; or patients with stage I or stage II disease with one of the following additional criteria: B-symptoms, or disease that is not radio- encompassable within a single involved field, or not a candidate for brief chemotherapy and irradiation, or the presence of bulky disease (any single mass =\> 10 cm)
* Previously untreated or treated with up to 3 cycles of standard dose 3- weekly R-CHOP chemotherapy prior to enrollment (i.e. patients may be enrolled prior to initiation of the fourth cycle of R-CHOP chemotherapy)
* ECOG Performance Status 0,1 or 2 at time of enrollment
* No evidence of progressive disease while on R-CHOP chemotherapy
* The patient must sign the consent form prior to registration

Exclusion Criteria:

* Patients with a history of any other lymphoproliferative disorder, including prior history of indolent NHL
* Patients with a history of prior or concurrent malignancies within 5 years of the current diagnosis, except adequately treated non- melanoma skin cancer, and curatively treated in-situ cancer of the cervix
* Known HIV infection
* Known hepatitis B virus infection
* Pregnancy or lactation. Men and women of childbearing age must be using adequate contraception.
* Significant renal insufficiency (serum creatinine \> 200 mmol/L), unless due to lymphoma
* Significant hepatic insufficiency (serum total bilirubin \> 30 mmol/L), unless due to lymphoma
* Cardiac contraindication to doxorubicin therapy (e.g. abnormal contractility on echocardiography). If history of cardiac disease, ejection fraction must be within normal limits for age.
* Neurologic contraindication to vincristine (e.g. peripheral neuropathy)
* Absolute neutrophil count \<1.5 x 109/L (unless due to bone marrow involvement with lymphoma or due to initiation of R-CHOP chemotherapy)
* Platelet count \< 100 x 109/L (unless due to splenomegaly, bone marrow involvement with lymphoma or due to initiation of R-CHOP chemotherapy)
* Evidence of active systemic infection
* Any medical condition that in the opinion of the investigator would compromise treatment delivery, add toxicity or impair assessment

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