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Clinical Trials (PDQ®)

  • First Published: 1/1/1998
  • Last Modified: 8/27/2010

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Clinical Trials (PDQ®)

Phase III Randomized Study of CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) With or Without Rituximab in Older Patients With Diffuse Mixed, Diffuse Large, or Immunoblastic Large Cell Non-Hodgkin's Lymphoma

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

Alternate Title

Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Older Patients With Non-Hodgkin's Lymphoma

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted60 and overNCIECOG-E4494
E4494, CLB-9793, SWOG-E4494, NCT00003150

Objectives

I. Compare the efficacy of CHOP (cyclophosphamide, doxorubicin, vincristine, 
and prednisone) with or without rituximab in older patients with diffuse 
mixed, diffuse large, or immunoblastic large cell non-Hodgkin's lymphoma of 
B-cell lineage with respect to the response rate, time to treatment failure, 
toxicity, and survival.

II. Compare the efficacy of maintenance therapy consisting of rituximab vs 
observation alone after initial therapy with respect to the time to treatment 
failure, duration of response, toxicity, and survival of this patient 
population.

III. Determine if maintenance therapy with rituximab results in the conversion 
of any partial response to complete response.

Entry Criteria

Disease Characteristics:


Histologically proven intermediate or high grade B-cell non-Hodgkin's
lymphoma (other than Burkitt's, non-Burkitt's, undifferentiated, or
lymphoblastic lymphoma)  
  B-cell non-Hodgkin's lymphoma positive for CD19 and/or CD20 by slide-based
   immunohistochemistry or flow cytometry

No mantle cell or follicular lymphoma 

Measurable disease, defined by at least one of the following:
 Physical examination 
 Radiographic findings of at least 2 dimensions
 Bidimensional measurable defect or mass measuring at least 2 cm in diameter
  on radionuclide or CT scan
 Enlarged spleen extending at least 2 cm below the costal margin provided
  that there is no other likely explanation besides lymphomatous involvement
 Enlarged liver extending at least 5 cm below the costal margin along with
  biopsy-proven lymphomatous hepatic involvement  

No history of transformed lymphoma

No known posttransplantation lymphoproliferative disorder

No CNS involvement

CALGB patients 60-65 years of age must not be eligible for any other study of
higher priority 

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.


Prior/Concurrent Therapy:


Biologic therapy:
 See Disease Characteristics
 No prior biologic response modifier therapy
 No prior immunotherapy
 No prior rituximab

Chemotherapy:
 No prior cytotoxic chemotherapy
 No concurrent dexrazoxane

Endocrine therapy:
 Prior corticosteroids allowed

Radiotherapy:
 No prior radiotherapy
 No prior radioimmunotherapy

Surgery:
 Not specified


Patient Characteristics:


Age:
 See Disease Characteristics
 60 and over

Performance status:
 ECOG 0-3

Life expectancy:
 Not specified

Hematopoietic:
 Absolute granulocyte count at least 1,500/mm3 (unless due to lymphoma)
 Platelet count greater than 100,000/mm3 (unless due to lymphoma)

Hepatic: 
 Bilirubin no greater than 3.0 mg/dL

Renal:
 Creatinine less than 2.1 mg/dL OR
 Creatinine clearance at least 60 mL/min

Cardiovascular:
 No active heart disease including congestive heart failure, myocardial
  infarction within the past 3 months, or symptomatic ventricular arrhythmia
 LVEF at least 45% if prior history of heart disease exists

Other:
 HIV negative
 No other malignancy within the past 5 years except squamous cell or basal
  cell skin cancer or carcinoma in situ of the cervix 

Expected Enrollment

630

Approximately 630 patients will be accrued for this study within 4 years.

Outline

This is a randomized study.  For the first randomization, patients are 
stratified according to the number of risk factors (0-1 vs 2-4).  For the 
second randomization, in addition to the number of risk factors, patients are 
stratified according to objective response to initial induction therapy 
(partial response vs complete response) and induction therapy (CHOP vs CHOP 
and rituximab).  Patients are randomized to one of two treatment arms.

Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, 
doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. 
Treatment repeats every 21 days in the absence of unacceptable toxicity.  

Arm II: Patients receive treatment as in arm I.  Patients also receive 
rituximab IV on days -7,-3, 41, and 83. 

Patients who achieve complete response (CR) after 4 courses of CHOP and remain 
in CR after 6 courses of CHOP are further randomized to one of two arms.

Arm I (Maintenance therapy): Patients receive rituximab IV weekly for 4 weeks. 
 Courses repeat every 6 months for 2 years in the absence of unacceptable 
toxicity.

Arm II:  Patients are observed.

Patients who achieve partial response (PR) after 6 courses OR PR after 4 
courses and then CR after 6 courses receive 2 additional courses of CHOP 
therapy.  Patients are then also randomized to receive either maintenance 
therapy or observation as above.  Patients with stable disease or disease 
progression are removed from the study.

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

Published Results

Advani RH, Chen H, Habermann TM, et al.: Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). Br J Haematol 151 (2): 143-51, 2010.[PUBMED Abstract]

Winter JN, Li S, Aurora V, et al.: Expression of p21 protein predicts clinical outcome in DLBCL patients older than 60 years treated with R-CHOP but not CHOP: a prospective ECOG and Southwest Oncology Group correlative study on E4494. Clin Cancer Res 16 (8): 2435-42, 2010.[PUBMED Abstract]

Aurora V, Li S, Horning SJ, et al.: Prognostic significance of p53/p21 expression in DLBCL treated with CHOP or R-CHOP: a correlative study of E4494. [Abstract] J Clin Oncol 25 (Suppl 18): A-8038, 450s, 2007.

Morrison VA, Weller EA, Habermann TM, et al.: Maintenance rituximab (MR) compared to observation (OBS) after R-CHOP or CHOP in older patients (pts) with diffuse large B-cell lymphoma (DLBCL): an Intergroup E4494/C9793 update. [Abstract] J Clin Oncol 25 (Suppl 18): A-8011, 443s, 2007.

Advani RH, Chen H, Habermann TM, et al.: Prognostic indices in older DLBCL patients receiving R-CHOP: an analysis of the U.S. Intergroup study (E4494, CALGB 9793). [Abstract] Blood 108 (11): A-813, 2006.

Habermann TM, Weller EA, Morrison VA, et al.: Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24 (19): 3121-7, 2006.[PUBMED Abstract]

Winter JN, Weller EA, Horning SJ, et al.: Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Blood 107 (11): 4207-13, 2006.[PUBMED Abstract]

Morrison V, Weller E, Habermann T, et al.: Dose intensity of CHOP alone or with rituximab in diffuse large B-cell lymphoma (DLBCL) in patients >60 years of age: an analysis of the intergroup trial ( CALGB 9793, ECOG-SWOG 4494). [Abstract] Ann Oncol 16 (Suppl 5): A-224, v102, 2005.

Habermann TM, Weller E, Morrison VA, et al.: Rituximab-CHOP versus CHOP with or without maintenance rituximab in patients 60 years of age or older with diffuse large B-cell lymphoma (DLBCL): an update. [Abstract] Blood 104 (11): A-127, 2004.

Morrison VA, Weller EA, Habermann TM, et al.: Patterns of growth factor (GF) usage and febrile neutropenia (FN) among older patients (pts) with diffuse large B-cell lymphoma (DLBCL) treated with CHOP or R-CHOP: an intergroup experience (CALGB 9793, ECOG-SWOG 4494). [Abstract] Blood 104 (11): A-3309, 2004.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Thomas Habermann, MD, Protocol chair
Ph: 507-284-2511

Cancer and Leukemia Group B

Vicki Morrison, MD, Protocol chair
Ph: 612-467-4135; 866-414-5058

Southwest Oncology Group

James Weick, MD, Protocol chair
Ph: 561-965-1864
Email: jweick@aol.com

Registry Information
Official Title Phase III Trial of CHOP Versus CHOP and Chimeric Anti-CD20 Monoclonal Antibody (IDEC-C2B8) in Older Patients with Diffuse Mixed, Diffuse Large Cell and Immunoblastic Large Cell Histology Non-Hodgkin's Lymphoma
Trial Start Date 1997-12-12
Registered in ClinicalTrials.gov NCT00003150
Date Submitted to PDQ 1997-11-24
Information Last Verified 2010-08-27
NCI Grant/Contract Number CA21115

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

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