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

Phase II Trial Investigating Tailoring First-Line Therapy For Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Mid-Treatment Positron Emission Tomography (PET) Scan Results

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.

This is a phase II trial investigating tailoring first-line therapy for advanced stage diffuse large B-cell NHL (DLBCL) based on a mid-treatment 18F-FDG- positron-emission tomography (PET) scan result. More than half of all patients with DLBCL can be cured with 6-8 cycles of standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Patients who are not cured with R-CHOP have a very poor prognosis. This study will 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).

Objectives:

• To assess the efficacy of tailoring first-line therapy based on a mid- treatment PET scan result for patients with advanced stage DLBCL.
• To assess the progression-free survival (PFS) in patients with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy.
• To assess the overall survival (OS) in patients with advanced stage DLBCL who have a negative mid-treatment PET scan and receive standard therapy with six cycles of CHOP-R and patients with a positive mid-treatment PET scan who receive four cycles of CHOP-R followed by four cycles of R-ICE chemotherapy.

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