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

Lymphoma, Non-Hodgkin Clinical Trial

— LYTPET  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00324467
• Other study ID #: H06-00017
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 2006
• Est. completion date: December 2021

Study information

• Verified date: July 2021
• Source: British Columbia Cancer Agency
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Cyclophosphamide
Dose: 750 mg/m^2 Administration: IV infusion day 1 over 20-60 minutes Schedule: Cycle 1, 2, 3, 4, 5*, 6* (Week 1, 4, 7, 10, 14, 17) * Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan
• Doxorubicin
Dose: 50 mg/m^2 Administration: IV Push day 1 Schedule: Cycle 1, 2, 3, 4, 5*, 6* (Week 1, 4, 7, 10, 14, 17) * Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan
• Vincristine
Dose: 1.4 mg/m^2 Administration: IV Push day 1 Schedule: Cycle 1, 2, 3, 4, 5*, 6* (Week 1, 4, 7, 10, 14, 17) * Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan
• Prednisone
Dose: 45 mg/m^2 Administration: IV infusion day 1 (or day 2) over 90 minutes-8 hours Schedule: Cycle 1, 2, 3, 4, 5*, 6* (Week 1, 4, 7, 10, 14, 17) * Cycles 5 and 6 of R-CHOP will be administered only to patients with a negative mid-treatment PET scan
• Ondansetron
Premedication for R-CHOP Dose: 8 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy
• Dexamethasone
Premedication for R-CHOP Dose: 12 mg Route: PO Schedule: 15 min pre-CHOP chemotherapy
• Diphenhydramine
Premedication for R-CHOP Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
• Acetaminophen
Premedication for R-CHOP Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
• Ifosfamide
R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 5000 mg/m^2 (total dose per cycle) Administration: In 3 equally divided doses IV infusion days 1,2,3, over 2 hours Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)
• Mesna (IV)
R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 5000 mg/m^2 (total dose per cycle) Administration: In 3 equally divided doses IV infusion days 1,2,3 (with ifosfamide) over 2 hours Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)
• Mesna (oral)
R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 2 g Administration: PO 2h and 4h after ifosfamide infusion on days 1,2,3 Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)
• Carboplatin
R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 5 x (25+CrCl*) (maximum dose 800 mg) Administration: IV infusion day 1 over 1 hour Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23) *Carboplatin is dose via the Calvert formula with an AUC of 5, maximum dose 800 mg per cycle. Estimate Creatinine Clearance (CrCl)
• Etoposide
R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 100 mg/m^2 Administration: IV infusion day 1,2,3 over 30 minutes Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)
• Rituximab
R-ICE Chemotherapy Schedule (cycles repeated every 3 weeks) Dose: 375 mg/m^2 Administration: IV infusion day 1 (or day 2 or day 3) over 90 minutes-8 hours Schedule: Cycle 1, 2, 3, 4 (Week 14, 16, 20, 23)
• Ondansetron
Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily
• Dexamethasone
Premedication for R-ICE Dose: 8 mg Route: PO Schedule: 15 min pre-chemotherapy daily
• Diphenhydramine
Premedication for R-ICE Dose: 50 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion
• Acetaminophen
Premedication for R-ICE Dose: 650 mg Route: PO Schedule: Prior to rituximab and then q 4h during rituximab infusion

Other:
• PET Scan
Investigations: 18F-FDG-PET scan Timing: After 4 cycles of R-CHOP (days 21-28) and after 4 cycles of R-ICE (days 28-35)

Locations

Country	Name	City	State
Canada	BC Cancer Agency	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
British Columbia Cancer Agency	Hoffmann-La Roche

Country where clinical trial is conducted

Canada, 

References & Publications (33)

Anderson DR, Grillo-López A, Varns C, Chambers KS, Hanna N. Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma. Biochem Soc Trans. 1997 May;25(2):705-8. Review. — View Citation

Cabanillas F, Hagemeister FB, McLaughlin P, Velasquez WS, Riggs S, Fuller L, Smith T. Results of MIME salvage regimen for recurrent or refractory lymphoma. J Clin Oncol. 1987 Mar;5(3):407-12. — View Citation

Carr R, Barrington SF, Madan B, O'Doherty MJ, Saunders CA, van der Walt J, Timothy AR. Detection of lymphoma in bone marrow by whole-body positron emission tomography. Blood. 1998 May 1;91(9):3340-6. — View Citation

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. — View Citation

Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. — View Citation

Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. Epub 2005 May 2. — View Citation

Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med. 1993 Apr 8;328(14):1002-6. — View Citation

Habermann TM, Weller EA, Morrison VA, et al. Phase III trial of Rituximab-CHOP (R-CHOP) vs. CHOP with a second randomization to maintenance rituximab (MR) or observation in patients 60 years of age and older with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;102:6 abstr.

Haioun C, Itti E, Rahmouni A, Brice P, Rain JD, Belhadj K, Gaulard P, Garderet L, Lepage E, Reyes F, Meignan M. [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome. Blood. 2005 Aug 15;106(4):1376-81. Epub 2005 Apr 28. — View Citation

Hertzberg MS, Crombie C, Benson W, Taper J, Gottlieb D, Bradstock KF. Outpatient-based ifosfamide, carboplatin and etoposide (ICE) chemotherapy in transplant-eligible patients with non-Hodgkin's lymphoma and Hodgkin's disease. Ann Oncol. 2003;14 Suppl 1:i11-6. — View Citation

Hoh CK, Glaspy J, Rosen P, Dahlbom M, Lee SJ, Kunkel L, Hawkin RA, Maddahi J, Phelps ME. Whole-body FDG-PET imaging for staging of Hodgkin's disease and lymphoma. J Nucl Med. 1997 Mar;38(3):343-8. — View Citation

Hutchings M, Mikhaeel NG, Fields P, Nunan T, O'Doherty M, Timothy A. The prognostic value of early FDG-PET during treatment of lymphoma and potential use in response-adapted treatment strategies. Annals of Oncology. 2005;16:280a.

Jaffe ES, Harris NL, Stein H, Vardiman JW eds. World Health Organization Classification of Tumors. Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001.

Jerusalem G, Beguin Y, Fassotte MF, Najjar F, Paulus P, Rigo P, Fillet G. Whole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging. Blood. 1999 Jul 15;94(2):429-33. — View Citation

Juweid ME, Wiseman GA, Vose JM, Ritchie JM, Menda Y, Wooldridge JE, Mottaghy FM, Rohren EM, Blumstein NM, Stolpen A, Link BK, Reske SN, Graham MM, Cheson BD. Response assessment of aggressive non-Hodgkin's lymphoma by integrated International Workshop Criteria and fluorine-18-fluorodeoxyglucose positron emission tomography. J Clin Oncol. 2005 Jul 20;23(21):4652-61. Epub 2005 Apr 18. — View Citation

Kewalramani T, Zelenetz AD, Hedrick EE, Donnelly GB, Hunte S, Priovolos AC, Qin J, Lyons NC, Yahalom J, Nimer SD, Moskowitz CH. High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis. Blood. 2000 Oct 1;96(7):2399-404. — View Citation

Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. — View Citation

Kostakoglu L, Coleman M, Leonard JP, Kuji I, Zoe H, Goldsmith SJ. PET predicts prognosis after 1 cycle of chemotherapy in aggressive lymphoma and Hodgkin's disease. J Nucl Med. 2002 Aug;43(8):1018-27. — View Citation

McKelvey EM, Gottlieb JA, Wilson HE, Haut A, Talley RW, Stephens R, Lane M, Gamble JF, Jones SE, Grozea PN, Gutterman J, Coltman C, Moon TE. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484-93. — View Citation

Mikhaeel NG, Timothy AR, O'Doherty MJ, Hain S, Maisey MN. 18-FDG-PET as a prognostic indicator in the treatment of aggressive Non-Hodgkin's Lymphoma-comparison with CT. Leuk Lymphoma. 2000 Nov;39(5-6):543-53. — View Citation

Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD. Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3776-85. — View Citation

Naumann R, Vaic A, Beuthien-Baumann B, Bredow J, Kropp J, Kittner T, Franke WG, Ehninger G. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol. 2001 Dec;115(4):793-800. — View Citation

Pfreundschuh M, Trumper L, Gill D, et al. First analysis of the completed Mabthera International (MInT) Trial in young patients with low-risk diffuse large B-cell lymphoma (DLBCL): Addition of rituximab to a CHOP-like regimen significantly improves outcome of all patients with the identification of a very favorable subgroup with IPI=0 and no bulky disease. Blood. 2004;104:48a.

Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. — View Citation

Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. — View Citation

Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O'Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol. 2005 Aug 1;23(22):5027-33. Epub 2005 Jun 13. — View Citation

Spaepen K, Stroobants S, Dupont P, Van Steenweghen S, Thomas J, Vandenberghe P, Vanuytsel L, Bormans G, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G. Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods? J Clin Oncol. 2001 Jan 15;19(2):414-9. — View Citation

Spaepen K, Stroobants S, Dupont P, Vandenberghe P, Thomas J, de Groot T, Balzarini J, De Wolf-Peeters C, Mortelmans L, Verhoef G. Early restaging positron emission tomography with ( 18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Sep;13(9):1356-63. — View Citation

Velasquez WS, Cabanillas F, Salvador P, McLaughlin P, Fridrik M, Tucker S, Jagannath S, Hagemeister FB, Redman JR, Swan F, et al. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood. 1988 Jan;71(1):117-22. — View Citation

Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F. ESHAP--an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol. 1994 Jun;12(6):1169-76. — View Citation

Vose J, Sneller V. Outpatient regimen rituximab plus ifosfamide, carboplatin and etoposide (R-ICE) for relapsed non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i17-20. Erratum in: Ann Oncol. 2004 Mar;15(3):541. — View Citation

Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. Review. — View Citation

Zinzani PL, Fanti S, Battista G, Tani M, Castellucci P, Stefoni V, Alinari L, Farsad M, Musuraca G, Gabriele A, Marchi E, Nanni C, Canini R, Monetti N, Baccarani M. Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients. Br J Cancer. 2004 Aug 31;91(5):850-4. — View Citation

* Note: There are 33 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) in participants with advanced stage DLBCL	Progression-free survival (PFS) in participants 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.; Progression-free survival is defined as the duration of time from diagnosis to time of disease progression or death from any cause. Living patients who have remained free of progression will have their PFS censored on the date last known alive.	Estimated two years
Secondary	Overall survival (OS) in participants with advanced stage DLBCL	Overall survival (OS) in participants 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.; Overall survival will be defined as the time from diagnosis to the date of death. If the participant is lost to follow-up, survival will be censored on the last date the participant was known to be alive.	Several years
Secondary	The safety of R-ICE therapy in first-line therapy of DLBCL following four cycles of R-CHOP as assessed using the NCI Common Terminology Criteria for Adverse Events Version 3.0		Six months
Secondary	Investigate clinical and biologic markers that characterize participant heterogeneity and may serve as predictors of response to therapy and overall outcome.	A central pathology review of original diagnostic biopsies will be performed by pathologists at the Coordinating Center to ensure appropriate lymphoma subclassification. This centralized review is not required prior to enrollment, provided the patients biopsy has been carefully reviewed by local pathologists and determined to be DLBCL.; Correlative studies of biologic markers will be performed on cases with adequately preserved tissue to explore the biologic heterogeneity between patients and to investigate determinants of response to therapy.	1 year
Secondary	Efficacy of tailoring first-line therapy bases on a mid-treatment PET scan result for patients with advanced stage DLBCL	All patients will have their BEST RESPONSE on study classified as outlined below. For patients with more than six measurable lesions the six most distinctly measurable at diagnosis should be chosen for response assessment by CT scanning. If available, lesions from both above and below the diaphragm should be chosen, at least two from each region.	Four to six months