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

Eastern Cooperative Oncology Group

Status and phase: Completed; Phase 3

Conditions: Lymphoma

Treatments: Biological: rituximab

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00075946

CDR0000346359

U10CA021115 (U.S. NIH Grant/Contract)

ECOG-E4402 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 545 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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545 participants in 2 patient groups

Arm A: Rituximab Retreatment

Active Comparator group

Description:

Patients receive rituximab IV once a week for 4 weeks upon disease progression provided time to progression is more than 6 months.

Treatment:

Biological: rituximab

Arm B: Rituximab Scheduled

Experimental group

Description:

Patients receive a single dose of rituximab IV once every 13 weeks until disease progression and in the absence of unacceptable toxicity.

Treatment:

Biological: rituximab