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NCT00075946 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2024-02-01

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Time to Rituximab Failure (TTRF)

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outcome · POSTED

Time to First Cytotoxic Therapy (TTFC)

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outcome · POSTED

Overall Health-related Quality of Life (HRQL) at 6 Month After Randomization

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.
    intervention Names
    1. Biological: rituximab
    label
    Arm A: Rituximab Retreatment
    type
    ACTIVE_COMPARATOR
  2. description
    Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.
    intervention Names
    1. Biological: rituximab
    label
    Arm B: Rituximab Scheduled
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm A: Rituximab Retreatment
    2. Arm B: Rituximab Scheduled
    description
    Given IV
    name
    rituximab
    type
    BIOLOGICAL
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
545
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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).
    measure
    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.
secondary Outcomes
  1. description
    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.
    measure
    Time to First Cytotoxic Therapy (TTFC)
    time Frame
    Assessed every 13 weeks until rituximab failure observed or August 2013, whichever occurred first.
  2. description
    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.
    measure
    Overall Health-related Quality of Life (HRQL) at 6 Month After Randomization
    time Frame
    Assessed at baseline and 6 months after randomization.
Full study description
brief Summary
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.
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.
Source references
references
  1. citation
    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.
    type
    RESULT
  2. citation
    Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402. J Clin Oncol. 2014 Oct 1;32(28):3096-102. doi: 10.1200/JCO.2014.56.5853. Epub 2014 Aug 25.
    pmid
    25154829
    type
    RESULT
  3. citation
    Rutherford SC, Yin J, Pederson L, Perez Burbano G, LaPlant B, Shadman M, Li H, LeBlanc ML, Kenkre VP, Hong F, Blum KA, Dockter T, Martin P, Jung SH, Grant B, Rosenbaum C, Ujjani C, Barr PM, Unger JM, Cheson BD, Bartlett NL, Kahl B, Friedberg JW, Mandrekar SJ, Leonard JP. Relevance of Bone Marrow Biopsies for Response Assessment in US National Cancer Institute National Clinical Trials Network Follicular Lymphoma Clinical Trials. J Clin Oncol. 2023 Jan 10;41(2):336-342. doi: 10.1200/JCO.21.02301. Epub 2022 Jul 5.
    pmid
    35787017
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        d="_1658" tabindex="-1">Standard therapy includes rituximab, an anti&#8211;CD20 monoclonal antibody, either alone, as was shown in the <a href="/clinicaltrials/NCT00075946">ECOG-E4402</a> trial (NCT00075946),[<a href="#cit/section_7.14">14</a>-<a href="#cit/section_7.19">19</a>] or in combination with purine nucleoside analogues,
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        erapy includes rituximab, an anti&#8211;CD20 monoclonal antibody, either alone, as was shown in the <a href="/clinicaltrials/NCT00075946">ECOG-E4402</a> trial (NCT00075946),[<a href="#cit/section_7.14">14</a>-<a href="#cit/section_7.19">19</a>] or in combination with purine nucleoside analogues, such as fludarabine or cladribine,
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        ctive of OS and histological transformation rates, no benefit could be seen with rituximab maintenance.</li></ul></div></li><li>In the <a href="/clinicaltrials/NCT00075946">RESORT</a> study (NCT00075946), 289 previously untreated patients with asymptomatic, low-burden disease were randomly assigned to receive rituximab induction
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        ansformation rates, no benefit could be seen with rituximab maintenance.</li></ul></div></li><li>In the <a href="/clinicaltrials/NCT00075946">RESORT</a> study (NCT00075946), 289 previously untreated patients with asymptomatic, low-burden disease were randomly assigned to receive rituximab induction alone, with a re-treatment stra
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      source update dates
      1. context
        Updated: May 14, 2025
        datetime
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        display
        May 14, 2025

    Preserved source evidence · Independent clinical review pending · Not medical advice