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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00075946
First received: January 12, 2004
Last updated: June 3, 2015
Last verified: June 2015
  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
Biological: rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial Comparing Two Different Rituximab Dosing Regimens For Patients With Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Time to Rituximab Failure (TTRF) [ Time Frame: Assessed (by restaging CT scans) 26 weeks ± 2 weeks from each rituximab treatment (including induction), counting the first rituximab dose as Day 1, until rituximab failure observed or July 17, 2013, whichever occurred first. ] [ Designated as safety issue: No ]
    TTRF is defined as the time from randomization until any one of the following criteria are met, and censored at last disease assessment for cases who have not experienced failure (with the cut-off date for final analysis of 11/1/2011): 1. No response (partial response (PR) or complete response (CR)) to rituximab retreatment (Arm A treatment). 2. Time to progression < 26 weeks from day 1 of most recent rituximab treatment. 3. Initiation of alternative therapy. 4. Inability to complete protocol therapy (due to adverse events, patient preference, or any other reason, including death).


Secondary Outcome Measures:
  • Time to First Cytotoxic Therapy (TTFC) [ Time Frame: Assessed every 13 weeks until rituximab failure observed or August 2013, whichever occurred first. ] [ Designated as safety issue: No ]
    TTFC is defined as the time from randomization to the time of first cytotoxic therapy (chemo and radio therapy), and censored as last follow-up time if no cytotoxic therapy has been used. Since median TTFC was not reached in 3 out of the 4 groups, 3-year TTFC was reported which was defined as the probability of not starting first cytotoxic therapy at 3 years.

  • Overall Health-related Quality of Life (HRQL) at 6 Month After Randomization [ Time Frame: Assessed at baseline and 6 months after randomization. ] [ Designated as safety issue: No ]
    The overall HRQL was measured by the change in Functional Assessment of Cancer Therapy - General (FACT-G) from baseline to 6 months after randomization. The FACT-G is a 27-item assessment used to measure HRQL, specifically, physical, functional, social and emotional well-being. The total score ranges from 0 to 108, with higher scores indicating better HRQL.


Enrollment: 545
Study Start Date: November 2003
Estimated Study Completion Date: September 2023
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A: Rituximab Retreatment
Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.
Biological: rituximab
Given IV
Experimental: Arm B: Rituximab Scheduled
Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.
Biological: rituximab
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To compare time to rituximab failure between the rituximab scheduled and rituximab retreatment arms.

Secondary

  • To compare the time to first cytotoxic therapy between the rituximab scheduled and rituximab retreatment arms.
  • To document the rationale for beginning cytotoxic therapy; defined as chemotherapy, radiation therapy or radioimmunotherapy.
  • To compare the toxicities associated with rituximab therapy between the two randomized treatment arms.
  • Quality of Life Objectives:

    1. To compare health-related quality of life, distress, psychological functioning, physical well-being and functional well-being of patients receiving rituximab scheduled to those receiving rituximab retreatment.
    2. To examine the impact of differential treatment response (delayed time to rituximab failure and/or time to first cytotoxic therapy), if observed, on quality of life, distress, and psychological functioning on patients receiving rituximab scheduled to those receiving rituximab retreatment.
    3. To obtain prospective data on physical and functional well-being during treatment with rituximab.

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 Intravenous (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 A (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 B (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.

  Eligibility

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

INCLUSION CRITERIA:

  • 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)
  • 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 a computed tomography (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 positron emission tomography (PET) scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging
  • Age: 18 and over
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Must meet the following criteria for labs:

    • Hematopoietic

      • 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
      • The aspartate transaminase (AST) and alanine transaminase (ALT) ratio (AST/ALT) no greater than 5 times ULN
      • Hepatitis B surface antigen negative
    • Renal

      • Creatinine no greater than 2 times ULN

EXCLUSION CRITERIA:

  • Evidence of transformation to a large cell histology
  • Pregnant or nursing. Fertile patients must use effective contraception
  • HIV positive
  • Uncontrolled active infection
  • 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 immunotherapy for lymphoma
  • Prior chemotherapy for lymphoma
  • Concurrent chemotherapy
  • Prior radiotherapy for lymphoma
  • Concurrent radiotherapy
  • Concurrent radioimmunotherapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 483 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Brad S. Kahl, MD University of Wisconsin, Madison
  More Information

Additional Information:
Publications:
Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00075946     History of Changes
Other Study ID Numbers: CDR0000346359, U10CA021115, ECOG-E4402
Study First Received: January 12, 2004
Results First Received: February 9, 2015
Last Updated: June 3, 2015
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on August 31, 2015