tailoring treatment for b cell non-hodgkin's lymphoma based on pet scan results mid treatment

Conditions: Lymphoma, Non-Hodgkin; Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Summary: 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.

Eligibility criteria:
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

Keywords: non-hodgkin's lymphoma positron emission tomography pet dlbcl r-chop r-ice