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

Alternate Title

Rituximab in Treating Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	ECOG-E4402 E4402, NCT00075946

Objectives

Primary

1. Compare the time to rituximab failure in patients with low tumor burden indolent non-Hodgkin's lymphoma treated with rituximab scheduled vs rituximab retreatment.

Secondary

1. Compare the time to first cytotoxic therapy in patients treated with these regimens.
2. Determine the rationale for beginning cytotoxic therapy, defined as chemotherapy, radiotherapy, or radioimmunotherapy, in patients treated with these regimens.
3. Compare the toxic effects associated with these regimens in these patients.
4. Correlate response and duration of response in these patients with rituximab pharmacokinetics.
5. Compare the health-related quality of life, distress, psychological functioning, physical well-being, and functional well-being of patients treated with these regimens.
6. Compare the impact of differential treatment response (delayed time to rituximab failure and/or time to first cytotoxic therapy) on quality of life, distress, and psychological functioning in patients treated with these regimens.
7. Determine, prospectively, the physical and functional well-being of patients during treatment with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed non-Hodgkin's lymphoma, including 1 of the following:
  • Follicular grade 1 or 2
  • Small lymphocytic
  • Marginal zone (nodal)
  • Marginal zone (splenic)
  • Mucosa-associated lymphoid tissue (MALT)



• No evidence of transformation to a large cell histology



• Stage III or IV disease



• Must meet the following criteria for low tumor burden:
  • No nodal or extranodal mass at least 7 cm
  • Less than 3 nodal masses greater than 3 cm in diameter
  • No systemic symptoms or B symptoms
  • No splenomegaly greater than 16 cm by CT scan
  • No evidence of risk of compression of a vital organ (i.e., ureteral or epidural)
  • No leukemic phase with greater than 5,000/mm³ circulating lymphocytes
  • No cytopenias, defined as any of the following:
    • Platelet count less than 100,000/mm³
    • Hemoglobin less than 10 g/dL
    • Absolute neutrophil count less than 1,500/mm³



• At least 1 objective measurable disease parameter
  • Abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging

Prior/Concurrent Therapy:

Biologic therapy

• See Radiotherapy
• No prior immunotherapy for lymphoma

Chemotherapy

• No prior chemotherapy for lymphoma
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for lymphoma
• No concurrent radiotherapy
• No concurrent radioimmunotherapy

Surgery

• Not specified

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,500/mm^3*
• Hemoglobin at least 10 g/dL*
• Platelet count at least 100,000/mm^3*

 [Note: *Without growth factor and/or transfusion support]

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN) OR direct bilirubin normal for patients with Gilbert's Syndrome
• AST/ALT no greater than 5 times ULN
• Hepatitis B surface antigen negative

Renal

• Creatinine no greater than 2 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No uncontrolled active infection
  • Afebrile for at least 48 hours off antibiotics
• No other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Expected Enrollment

A total of 389 patients will be accrued for this study within 45 months.

Outcomes

Time to treatment failure

Time to first cytotoxic therapy

Outline

This is a randomized, multicenter study. Patients are stratified according to histologic subtype (follicular vs other), age (under 60 vs 60 and over), and the time from diagnosis (less than 1 year vs at least 1 year).

• Induction rituximab: Patients receive rituximab IV once a week for 4 weeks.

Patients are re-evaluated 9 weeks after the completion of induction rituximab. Patients with a partial or complete response to induction rituximab are randomized to 1 of 2 treatment arms.

• Arm I (retreatment rituximab): Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.



• Arm II (scheduled rituximab): Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.

Quality of life is assessed after induction rituximab treatment and at 26, 39, 65, 117, 169, and 221 weeks after randomization.

Patients are followed at least annually for 15 years from study entry.

Kahl BS, Williams ME, Hong F, et al.: Preliminary pharmacokinetic (PK) analysis of Eastern Cooperative Oncology Group Protocol E4402: rituximab extended schedule or re-treatment trial (RESORT) . [Abstract] Blood 110 (11): A-3420, 2007.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Brad Kahl, MD, Protocol chair		Ph: 608-263-1836; 800-622-8922 Email: bkahl@facstaff.wisc.edu
Michael Williams, MD, Protocol co-chair		Ph: 434-924-9637; 800-223-9173 Email: Mew4p@virginia.edu

Registry Information
Official Title		Randomized Phase III Trial Comparing Two Different Rituximab Dosing Regimens For Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma
Trial Start Date		2003-11-21
Trial Completion Date		2010-04-01 (estimated)
Registered in ClinicalTrials.gov		NCT00075946
Date Submitted to PDQ		2003-11-12
Information Last Verified		2008-10-22
NCI Grant/Contract Number		CA21115

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