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

Alternate Title

Combination Chemotherapy With Monoclonal Antibody Therapy in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	SWOG-S0016 CALGB-50102, S0016, NCT00006721, ECOG-SWOG-S0016

Special Category: CTSU trial

Objectives

1. Compare the progression-free survival and overall survival of patients with newly diagnosed follicular non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with or without either rituximab or iodine I 131 tositumomab (monoclonal antibody anti-B1). (CHOP chemotherapy alone arm closed to accrual as of 12/15/02)
2. Compare the response rate of these patients treated with these regimens.
3. Compare the toxic effects of these regimens in these patients.
4. Compare the molecular remission rates of this patient population treated with these regimens.
5. Determine the incidence and time to development of human anti-mouse antibody positivity.

Entry Criteria

Disease Characteristics:

• Histologically confirmed previously untreated bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma
  • Grade I-III disease



• CD20 antigen positive



• Fewer than 5,000/mm³ circulating lymphoid cells on a WBC differential count



• Bidimensionally measurable disease



• Bone marrow aspiration and biopsy within the past 42 days



• No clinical evidence of CNS involvement by lymphoma

Prior/Concurrent Therapy:

Biologic therapy:

• No prior monoclonal antibodies for cancer

Chemotherapy:

• No prior chemotherapy for lymphoma
  • Prior prednisone for non-lymphoma related illnesses allowed

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for lymphoma

Surgery:

• See Disease Characteristics

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Granulocyte count greater than 1,500/mm³
• Platelet count greater than 100,000/mm³

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No impaired cardiac status, including:
  • Severe coronary artery disease
  • Cardiomyopathy
  • Congestive heart failure
  • Serious arrhythmia
• Ejection fraction at least lower limit of normal by MUGA or 2-D echocardiogram for questionable cardiac history

Other:

• No hypersensitivity to iodine
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 6 months after study participation
• HIV negative
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Expected Enrollment

Approximately 500 patients (250 per treatment arm) will be accrued for this study within 5.5 years. (Arm I closed to accrual as of 12/15/02)

Outcomes

Compare progression-free survival rates of patients treated with CHOP chemotherapy alone, CHOP with rituximab, or CHOP followed by iodine-131 anti-CD20 antibody by Kaplan Meier survival curves at 2 or 5 years

Compare response rates (confirmed and unconfirmed complete and partial responses) by Cheson criteria at 4 weeks and 6 months after completion of therapy and then annually
Compare toxicities by NCI CTC at 4 weeks and 6 months after completion of therapy and then annually

Outline

This is a randomized, multicenter study. Patients are stratified according to whether microglobulin is greater than upper limit of normal (yes vs no). Patients are randomized to 1 of 3 treatment arms. (Arm I closed to accrual as of 12/15/02)

• Arm I (CHOP only): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1. Patients also receive oral prednisone daily on days 1-5. Treatment continues every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. (Arm I closed to accrual as of 12/15/02)



• Arm II (CHOP + rituximab): Patients receive cyclophosphamide IV over 15 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on days 8, 29, 50, 71, 92, and 113. Patients also receive oral prednisone daily on days 8-12, 29-33, 50-54, 71-75, and 113-117 and rituximab IV over 4-6 hours on days 1, 6, 48, 90, 134, and 141.



• Arm III (CHOP + tositumomab): Patients receive chemotherapy as in arm I and tositumomab (monoclonal antibody anti-B1) IV over 1 hour followed by iodine I 131 tositumomab IV over 20 minutes on days 134 and 141.

Patients are followed on day 200, at 1 year, every 6 months for 2 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Oliver Press, MD, PhD, Protocol chair		Ph: 206-667-1872 Email: press@u.washington.edu

Cancer and Leukemia Group B

Myron Czuczman, MD, Protocol chair		Ph: 716-845-3221; 800-685-6825 Email: Myron.Czuczman@roswellpark.org

Eastern Cooperative Oncology Group

Sandra Horning, MD, Protocol chair		Ph: 650-725-6456; 800-756-9000

Registry Information
Official Title		A Phase III Trial of CHOP Plus Rituximab vs CHOP Plus Iodine-131-Labeled Monoclonal Anti-B1 Antibody (Tositumomab) for Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphomas
Trial Start Date		2001-03-01
Trial Completion Date		2004-08-02 (estimated)
Registered in ClinicalTrials.gov		NCT00006721
Date Submitted to PDQ		2000-10-05
Information Last Verified		2009-01-12
NCI Grant/Contract Number		CA32102