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

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003150

Collaborator

National Cancer Institute (NCI) (NIH), Cancer and Leukemia Group B (Other), Southwest Oncology Group (Other)

630

Enrollment

Locations

105

Duration (Months)

6.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 if combination chemotherapy is more effective with or without rituximab for non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without rituximab in treating older patients who have non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate	Phase 3

Detailed Description

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.

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

630 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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

Study Start Date :

Dec 1, 1997

Actual Study Completion Date :

Sep 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - Gulf Coast	Mobile	Alabama	United States	36688
2	CCOP - Greater Phoenix	Phoenix	Arizona	United States	85006-2726
3	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona	United States	85012
4	Veterans Affairs Medical Center - Tucson	Tucson	Arizona	United States	85723
5	Arizona Cancer Center	Tucson	Arizona	United States	85724
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas	United States	72205
8	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California	United States	91010-3000
9	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
10	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0804
11	Veterans Affairs Medical Center - West Los Angeles	Los Angeles	California	United States	90073
12	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
13	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California	United States	94553
14	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
15	Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
16	University of California Davis Medical Center	Sacramento	California	United States	95817
17	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
18	David Grant Medical Center	Travis Air Force Base	California	United States	94535
19	University of Colorado Cancer Center	Denver	Colorado	United States	80010
20	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
21	Hematology Oncology Associates	Atlantis	Florida	United States	33462
22	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
23	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
24	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
25	MBCCOP - University of Illinois at Chicago	Chicago	Illinois	United States	60612-7323
26	CCOP - Central Illinois	Decatur	Illinois	United States	62526
27	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois	United States	60141
28	Loyola University Medical Center	Maywood	Illinois	United States	60153
29	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
30	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
31	Veterans Affairs Medical Center - Wichita	Wichita	Kansas	United States	67218
32	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40511-1093
33	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
34	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
35	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
36	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71130-3932
37	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71130
38	Boston Medical Center	Boston	Massachusetts	United States	02118
39	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
40	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105
41	CCOP - Ann Arbor Regional	Ann Arbor	Michigan	United States	48106
42	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
43	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
44	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201-1932
45	Henry Ford Hospital	Detroit	Michigan	United States	48202
46	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
47	Providence Hospital - Southfield	Southfield	Michigan	United States	48075-9975
48	CCOP - Duluth	Duluth	Minnesota	United States	55805
49	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi	United States	39531-2410
50	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
51	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
52	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi	United States	39534-2576
53	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri	United States	64128
54	CCOP - Kansas City	Kansas City	Missouri	United States	64131
55	St. Louis University Health Sciences Center	Saint Louis	Missouri	United States	63110-0250
56	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
57	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
58	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
59	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
60	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico	United States	87131
61	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
62	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
63	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
64	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
65	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
66	CCOP - Columbus	Columbus	Ohio	United States	43206
67	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
68	CCOP - Dayton	Kettering	Ohio	United States	45429
69	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio	United States	43623-3456
70	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma	United States	73104
71	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73190
72	Oregon Cancer Center	Portland	Oregon	United States	97201-3098
73	Veterans Affairs Medical Center - Portland	Portland	Oregon	United States	97207
74	CCOP - Columbia River Program	Portland	Oregon	United States	97213
75	CCOP - Greenville	Greenville	South Carolina	United States	29615
76	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
77	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
78	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
79	University of Texas Medical Branch	Galveston	Texas	United States	77555-0209
80	Texas Tech University Health Science Center	Lubbock	Texas	United States	79423
81	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
82	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78284
83	Veterans Affairs Medical Center - Temple	Temple	Texas	United States	76504
84	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
85	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
86	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah	United States	84148
87	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
88	Swedish Cancer Institute	Seattle	Washington	United States	98104
89	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
90	CCOP - Northwest	Tacoma	Washington	United States	98405-0986
91	Madigan Army Medical Center	Tacoma	Washington	United States	98431-5000

Sponsors and Collaborators

Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Cancer and Leukemia Group B
Southwest Oncology Group

Investigators

Study Chair: Thomas M. Habermann, MD, Mayo Clinic
Study Chair: Vicki A. Morrison, MD, Veterans Affairs Medical Center - Minneapolis
Study Chair: James K. Weick, MD, Hematology Oncology Associates of the Palm Beaches