Rituximab in Treating Patients With Follicular Non-Hodgkin's Lymphoma

Swiss Group for Clinical Cancer Research

Status and phase: Completed; Phase 3

Conditions: Lymphoma

Treatments: Biological: rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT00227695

CDR0000443594

EU-20520

SWS-SAKK-35/03

SAKK 35/03

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether giving rituximab over a short period of time is more effective than giving it over a long period of time in treating follicular non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab to see how well it works when given over a short period of time compared to when given over a long period of time in treating patients with follicular non-Hodgkin's lymphoma.

Full description

OBJECTIVES:

Primary

• Compare the efficacy of induction therapy with rituximab followed by short- vs long-term maintenance therapy with rituximab, in terms of event-free survival, in patients with follicular non-Hodgkin's lymphoma.

Secondary

• Compare the safety of these regimens in these patients.
• Compare the pharmaeconomical aspects of these regimens in these patients.
• Compare the evolution of immunologic competence in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

• Induction therapy: Patients receive rituximab IV weekly in weeks 1-4 and undergo restaging between weeks 11-13. Patients with stable disease or progressive disease are taken off study. Patients achieving partial or complete response are stratified according to prior treatment status (untreated* vs treated with or without anti-CD20 therapy), presence of bulky disease** at study entry (yes vs no), and participating center. Patients are then randomized to 1 of 2 maintenance treatment arms.

NOTE: *Patients treated with radiotherapy only are considered as therapy-naïve.

NOTE: **Defined as a mass or lymph node conglomerate ≥ 5 cm diameter.

• Maintenance therapy: Patients start maintenance therapy within 7 days of randomization.

  • Arm I: Patients receive rituximab IV every 2 months for 4 treatments.
  • Arm II: Patients receive rituximab IV every 2 months for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months until disease progression or relapse and then annually for up to 10 years after randomization.

PROJECTED ACCRUAL: A total of 270 patients will be accrued for this study within 3 years.

Enrollment: 270 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular lymphoma

  • Grade 1, 2, 3a, or 3b disease by WHO staging system

• CD20-positive by immunohistochemistry

• Previously untreated disease OR meets 1 of the following criteria for response to prior treatment:

  • Chemotherapy-resistant disease

  • Relapsed or progressive disease

  • Stable disease

    • At least 12 weeks since prior systemic treatment

• At least 1 bidimensionally measurable lesion ≥ 11 mm by CT scan or MRI

• No transformation to high-grade lymphoma secondary to low-grade follicular lymphoma

• No prior or current CNS disease (i.e., CNS lymphoma or lymphomatous meningosis) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• Ejection fraction ≥ 50% by echocardiography or MUGA

Immunologic

• No acute or ongoing infection
• No HIV infection
• No active autoimmune disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of the study treatment
• No uncontrolled diabetes mellitus
• No other medical condition that would preclude study participation
• No other malignancy except nonmelanoma skin cancer or adequately treated carcinoma in situ of the cervix
• No other condition (e.g., geographic proximity) that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Radiotherapy
• Prior rituximab allowed

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• More than 4 weeks since prior regular administration of corticosteroids

  • Dose equivalent to ≤ 20 mg/day prednisone allowed for conditions other than lymphoma or lymphoma-related symptoms

• No concurrent corticosteroids for prevention or treatment of side effects except acute life-threatening side effects

Radiotherapy

• Prior radiolabeled anti-CD20 therapy (administered alone or in combination with cytostatic drugs) allowed provided patient has achieved partial or complete response after the therapy

  • At least 12 months since prior anti-CD20 therapy

Surgery

• Not specified

Other

• More than 30 days since prior systemic tumor therapy
• More than 30 days since prior participation in another clinical trial
• No other concurrent anticancer therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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270 participants in 2 patient groups

Arm A: Rituximab every 2 months x4

Active Comparator group

Description:

Rituximab 375 mg/m2 every 2 months x4

Treatment:

Biological: rituximab

Arm B: Rituximab (5 years)

Active Comparator group

Description:

Rituximab 375 mg/m2 every 2 months for 5 years or until PD, relapse or unacceptable toxicity

Treatment:

Biological: rituximab