Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's lymphoma.
2. Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with these regimens.
3. 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.
4. Compare the safety and side effects of these regimens in these patients.

Secondary

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

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

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

Outcomes

Time to treatment failure at 3 years within the study and then periodically after study completion

Complete response rate at 3 years within the study and then periodically after study completion
Progression rate
Survival
Tumor control
Disease-free survival

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.

Pfreundschuh M, Schubert J, Ziepert M, et al.: Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 9 (2): 105-16, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

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

Michael Pfreundschuh, MD, Protocol chair		Ph: 49-6841-162-3084 Email: michael.pfreundschuh@uniklinik-saarland.de

Registry Information
Official Title		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
Trial Start Date		2001-01-04
Registered in ClinicalTrials.gov		NCT00052936
Date Submitted to PDQ		2002-11-12
Information Last Verified		2007-06-01

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