Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma
Randomised Study Comparing 6 And 8 Cycles Of Chemotherapy With CHOP ( Cyclophosphamide, Doxorubicin, Vincristine And Prednisone) At 14-Day Intervals (CHOP-14), Both With Or Without The Monoclonal Anti-CD20 Antibody Rituximab In Patients Aged 61 To 80 Years With Aggressive Non-Hodgkin's Lymphoma
  • Phase

    Phase 3
  • Study Type

  • Status

    Completed No Results Posted
  • Study Participants

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).


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.


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.
Study Started
Jan 31
Primary Completion
Aug 05
Study Completion
Aug 05
Last Update
May 18

Biological filgrastim

Biological rituximab

Drug CHOP regimen

Drug cyclophosphamide

Drug doxorubicin hydrochloride

Drug prednisone

Drug vincristine sulfate

Radiation radiation therapy

36Gy on BULK and extranodal involvement

S6 Experimental

6x CHOP-14

R6 Experimental

6x CHOP-14 + 8x Rituximab

S8 Experimental

8x CHOP-14

R8 Experimental

8x CHOP-14 + 8x Rituximab



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

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

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



61 to 80

Performance status

Karnofsky 60-100%

Life expectancy

Not specified


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


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


Creatinine no greater than 2 times ULN


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


FEV1 at least 50%
Diffusion capacity at least 50%


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


Biologic therapy

Not specified


No prior chemotherapy

Endocrine therapy

Not specified


No prior radiotherapy


Not specified


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
No Results Posted