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

German High-Grade Non-Hodgkin's Lymphoma Study Group

Status and phase: Completed; Phase 3

Conditions: Lymphoma

Treatments: Biological: rituximab; Drug: prednisone; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Radiation: radiation therapy; Biological: filgrastim; Drug: CHOP regimen; Drug: cyclophosphamide

Study type: Interventional

Funder types: Other

Identifiers

NCT00052936

EU-20243 (Other Identifier)

DSHNHL-1999-1A (Other Grant/Funding Number)

CDR0000269015

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 tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without rituximab in treating aggressive non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide, doxorubicin, vincristine, and prednisone together with or without rituximab works in treating older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer randomized as of 6/2005).

Full description

OBJECTIVES:

Primary

• Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma.
• Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens.
• Compare the rate of complete remission, rate of primary progression, tumor control, disease-free survival, overall survival, and relapse after radiotherapy in patients treated with these regimens.
• Compare the safety and side effects of these regimens in these patients.

Secondary

• Compare short-term and long-term side effects of these regimens in these patients.
• Compare quality of life of patients treated with these regimens.
• Compare the cost of these regimens in these patients.
• Determine relapse in patients treated with these regimens who received involved-field radiotherapy.

OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label, multicenter study. Patients are stratified according to participating center, value for serum lactic dehydrogenase (no greater than upper limit of normal [ULN] vs greater than ULN), bulky disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0 or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms. Patients with CD20-negative lymphoma are randomized to arms I or II only.

• Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to day 0 before initiating CHOP chemotherapy.
• Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses.
• Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm I for a total of 8 courses.
• Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.
• Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery of bone marrow, and after complete remision of mucositis, patients with sites of initial bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.

Enrollment: 1,506 patients

Sex: All

Ages: 61 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin's lymphoma (NHL) by an excisional biopsy of a lymph node or an extensive biopsy of an extranodal involvement (if there is no lymph node involvement)

• CD20^+ B-cell lymphoma or CD20^- B-cell and T-cell lymphoma allowed

• B-cell NHL including the following:

  • Stage III follicular lymphoma

  • Stage III follicular lymphoma and diffuse B-cell lymphoma

  • Lymphoblastic precursor B-cell lymphoma

  • Diffuse large cell B-cell lymphoma

    • Centroblastic
    • Immunoblastic
    • Plasmablastic
    • Anaplastic large cell
    • T-cell-rich B-cell lymphoma
    • Primary effusion lymphoma
    • Intravasal B-cell lymphoma
    • Primary mediastinal B-cell lymphoma

  • Mantle zone lymphoma, blastoid

  • Burkitt's lymphoma

  • Burkitt-like lymphoma

  • Aggressive marginal zone lymphoma (monocytoid)

• T-cell NHL including the following:

  • Lymphoblastic precursor T-cell lymphoma

  • Peripheral T-cell lymphoma (PTCL) not otherwise specified (NOS)

    • Lennert's lymphoma
    • T-zone lymphoma

  • T-cell lymphoma of the angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) type

  • Anaplastic large cell lymphoma

    • ALK^+
    • ALK^-

  • Extranodal NK/T-cell lymphoma, nasal type

  • Intestinal T/NK-cell lymphoma (with or without enteropathy)

    • Hepatosplenic gamma-delta lymphoma
    • Subcutaneous panniculitis-like PTCL
    • Aggressive T/NK PTCL

  • Anaplastic large-cell NHL, NOS

• Bone marrow involvement no more than 25%

• No lymphoma that is clearly restricted to the CNS or originating from the gastrointestinal tract

PATIENT CHARACTERISTICS:

Age

• 61 to 80

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• No active hepatitis infection

Renal

• Creatinine no greater than 2 times ULN

Cardiovascular

• No Canadian Cardiovascular Society class III or IV angina pectoris
• No New York Heart Association class III or IV cardiac failure
• Ejection fraction at least 50%
• Fractional shortenings at least 25% by echocardiography or nuclear medicine examination

Pulmonary

• FEV1 at least 50%
• Diffusion capacity at least 50%

Other

• No uncontrolled diabetes mellitus
• No known hypersensitivity to any study medications
• No other concurrent malignancy
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified

Other

• Must not have already initiated lymphoma therapy (except for the prephase treatment specified for this study)
• No other concurrent lymphoma therapy
• No concurrent participation in another treatment study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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1,506 participants in 4 patient groups

S6

Experimental group

Description:

6x CHOP-14

Treatment:

Radiation: radiation therapy

Biological: filgrastim

Drug: vincristine sulfate

Drug: CHOP regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: prednisone

R6

Experimental group

Description:

6x CHOP-14 + 8x Rituximab

Treatment:

Radiation: radiation therapy

Biological: filgrastim

Biological: rituximab

Drug: vincristine sulfate

Drug: CHOP regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: prednisone

S8

Experimental group

Description:

8x CHOP-14

Treatment:

Radiation: radiation therapy

Biological: filgrastim

Drug: vincristine sulfate

Drug: CHOP regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: prednisone

R8

Experimental group

Description:

8x CHOP-14 + 8x Rituximab

Treatment:

Radiation: radiation therapy

Biological: filgrastim

Biological: rituximab

Drug: vincristine sulfate

Drug: CHOP regimen

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: prednisone