Combination Chemotherapy With or Without Rituximab in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether chemotherapy is more effective with or without rituximab for relapsed non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is studying combination chemotherapy and rituximab to see how well they work compared to combination chemotherapy alone in treating patients with relapsed non-Hodgkin's lymphoma.

Sex

All

Minimum age

18 Years

Maximum age

120 Years

DISEASE CHARACTERISTICS:

* Histologically or cytologically proven stage III or IV follicular non-Hodgkin's lymphoma (NHL)

  * Relapsed after or no response (no change/progressive disease) to no more than 2 adequate non-anthracycline-containing systemic chemotherapy regimens
  * At least 2 months of single-agent therapy (e.g., chlorambucil) AND/OR
  * At least 2 consecutive courses of polychemotherapy (e.g., cyclophosphamide, vincristine, and prednisone) or purine analogues
* Complete or partial remission or no change for at least 4 weeks after completion of prior therapy OR progression during one of a maximum of 2 prior therapy regimens
* CD20 positive
* At least 1 bidimensionally measurable mass
* No greater than 10,000,000/mL circulating tumor cells
* IgG levels at least 3 g/L
* No low-grade NHL transformed into intermediate- or high-grade NHL
* No symptomatic CNS lymphoma
* No bone marrow involvement only NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Bilirubin less than 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase less than 2.5 times ULN

Renal:

* Creatinine less than 2.5 times ULN
* BUN less than 2.5 times ULN

Cardiovascular:

* No severe cardiac disease (i.e., severe heart failure requiring symptomatic treatment)

Pulmonary:

* No severe pulmonary disease

Other:

* No severe neurologic or psychiatric disease
* No severe metabolic disease
* Not pregnant
* Fertile patients must use effective contraception
* No prior malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or other cancer curatively treated with surgical therapy
* HIV negative
* No uncontrolled asthma or allergy requiring steroids
* No known hypersensitivity or prior anaphylactic reaction to murine proteins or any component of study drug

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior rituximab
* No prior allogeneic or autologous peripheral blood stem cell transplantation
* Concurrent filgrastim (G-CSF) for stem cell mobilization allowed

Chemotherapy:

* See Disease Characteristics
* No prior anthracyclines or mitoxantrone
* No concurrent chemotherapy for stem cell mobilization

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

• BACKGROUNDDeconinck E, Miadi-Fargier H, Pen CL, Brice P. Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation. Pharmacoeconomics. 2010;28(1):35-46. doi: 10.2165/11314070-000000000-00000. PMID 20014875
• BACKGROUNDPompen M, Huijgens PC, et al.: Cost-effectiveness of rituximab for maintenance in patients with follicular non-Hodgkin's lymphoma in the Dutch setting. [Abstract] Blood 112 (11): A-2364, 2008.
• BACKGROUNDVan Oers MH, Hagenbeek A, Van Glabbeke M, Teodorovic I. Chimeric anti-CD20 monoclonal antibody (Mabthera) in remission induction and maintenance treatment of relapsed follicular non-Hodgkin's lymphoma: a phase III randomized clinical trial--Intergroup Collaborative Study. Ann Hematol. 2002 Oct;81(10):553-7. doi: 10.1007/s00277-002-0548-2. Epub 2002 Oct 17. No abstract available. PMID 12424535
• RESULTvan Oers MH, Tonnissen E, Van Glabbeke M, Giurgea L, Jansen JH, Klasa R, Marcus RE, Wolf M, Kimby E, Vranovsky A, Holte H, Hagenbeek A, van der Reijden BA. BCL-2/IgH polymerase chain reaction status at the end of induction treatment is not predictive for progression-free survival in relapsed/resistant follicular lymphoma: results of a prospective randomized EORTC 20981 phase III intergroup study. J Clin Oncol. 2010 May 1;28(13):2246-52. doi: 10.1200/JCO.2009.25.0852. Epub 2010 Apr 5. PMID 20368567
• RESULTvan Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, Kimby E, van t Veer M, Vranovsky A, Holte H, Hagenbeek A. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010 Jun 10;28(17):2853-8. doi: 10.1200/JCO.2009.26.5827. Epub 2010 May 3. PMID 20439641
• RESULTvan Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, Jack A, Van't Veer M, Vranovsky A, Holte H, van Glabbeke M, Teodorovic I, Rozewicz C, Hagenbeek A. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006 Nov 15;108(10):3295-301. doi: 10.1182/blood-2006-05-021113. Epub 2006 Jul 27.