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

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Completed

Phase 3

Conditions

Lymphoma

Treatments

Drug: vincristine sulfate

Drug: cyclophosphamide

Drug: prednisone

Drug: CHOP regimen

Drug: doxorubicin hydrochloride

Biological: rituximab

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT00004179

ALLG-NHLLOW4 (Other Identifier)

BNLI-EORTC-20981 (Other Identifier)

EORTC-20981 (Other Identifier)

HOVON-H039 (Other Identifier)

CAN-NCIC-LY7 (Other Identifier)

NORDIC-EORTC-20981 (Other Identifier)

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Compare the response rate and quality of remission in patients with relapsed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without rituximab.
Compare the event-free survival and overall survival of patients treated with these regimens.
Determine the effect of rituximab as maintenance therapy on progression-free survival of these patients.

OUTLINE: This is a randomized, multicenter study.

Induction: Patients are randomized to one of two treatment arms. Patients are stratified according to participating center, prior treatment with purine analogues, age, number of prior induction treatments and best response obtained (complete vs partial remission vs no change/progressive disease), time since diagnosis (less than 2 years vs more than 2 years), and bulky disease (less than 10 cm vs greater than 10 cm).
- Arm I (closed as of 12/20/04): Patients receive induction chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5 (CHOP chemotherapy). Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive CHOP chemotherapy as in arm I. Rituximab IV is administered 1 hour after prednisone and before the IV drugs.
Maintenance: Patients who achieve partial or complete remission are then randomized to one of two treatment arms. Patients are stratified according to rituximab administration during induction (yes vs no), quality of the response (complete vs partial remission vs no change/progressive disease), and participating center.
- Arm I: Patients receive no further therapy.
- Arm II: Beginning 8 weeks after the last CHOP course, patients receive rituximab IV once every 3 months for up to 2 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 4 months thereafter.

PROJECTED ACCRUAL: A total of 752 patients will be accrued for this study within 6 years.

Enrollment

475 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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: