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

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00075946

Purpose

RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known which rituximab regimen is more effective in treating indolent non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and comparing them to see how well they work in treating patients with low tumor burden indolent stage III non-Hodgkin's lymphoma or stage IV non-Hodgkin's lymphoma.

Condition	Intervention	Phase
Lymphoma	Drug: rituximab	Phase III

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized Phase III Trial Comparing Two Different Rituximab Dosing Regimens For Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Time to treatment failure [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to first cytotoxic therapy [ Designated as safety issue: No ]

Estimated Enrollment:	389
Study Start Date:	November 2003
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.	Drug: rituximab Given IV
Arm II: Experimental Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.	Drug: rituximab Given IV

Detailed Description:

OBJECTIVES:

Primary

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

Compare the time to first cytotoxic therapy in patients treated with these regimens.
Determine the rationale for beginning cytotoxic therapy, defined as chemotherapy, radiotherapy, or radioimmunotherapy, in patients treated with these regimens.
Compare the toxic effects associated with these regimens in these patients.
Correlate response and duration of response in these patients with rituximab pharmacokinetics.
Compare the health-related quality of life, distress, psychological functioning, physical well-being, and functional well-being of patients treated with these regimens.
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.
Determine, prospectively, the physical and functional well-being of patients during treatment with these regimens.

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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/mm^3 circulating lymphocytes
- No cytopenias, defined as any of the following:
  - Platelet count less than 100,000/mm^3
  - Hemoglobin less than 10 g/dL
  - Absolute neutrophil count less than 1,500/mm^3
At least 1 objective measurable disease parameter
- Abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00075946

Show 484 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Brad S. Kahl, MD	University of Wisconsin, Madison
Investigator:	Michael E. Williams, MD	University of Virginia

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications of Results:

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.

Study ID Numbers:	CDR0000346359, ECOG-E4402
Study First Received:	January 12, 2004
Last Updated:	November 4, 2008
ClinicalTrials.gov Identifier:	NCT00075946
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma

stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell

Lymphatic Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
B-cell lymphomas
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Follicular lymphoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Physiological Effects of Drugs
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009