Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

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. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

Further Study Information

OBJECTIVES:

Primary

• Determine the 2-year progression-free survival (PFS) rate after treatment with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in patients with bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma who remain positron emission tomography (PET)-positive after 3 courses of rituximab, cyclophosphamide, vincristine, doxorubicin hydrochloride, and prednisone.

Secondary

• Determine the proportion of mid-treatment PET-positive patients who become PET-negative after 4 courses of R-ICE.

• Determine the PFS of mid-treatment PET-negative patients treated with these regimens.

• Determine the overall survival of patients treated with these regimens.

• Determine the toxicity of these regimens in these patients.

OUTLINE:

• Rituximab and CHOP chemotherapy (R-CHOP): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo fludeoxyglucose F18 positron emission tomography (PET) scanning and conventional restaging during course 3. Based on the PET results, patients are assigned to 1 of 2 treatment groups.

• Group I (PET negative): Patients receive 2 more courses of R-CHOP as above in the absence of disease progression or unacceptable toxicity.

• Group II (PET positive): Patients receive R-ICE comprising rituximab IV on day 1, ifosfamide IV continuously over 24 hours and carboplatin IV over 30 minutes on day 2, and etoposide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously once daily starting on day 4 and continuing until blood counts recover. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 10 years from the date of study entry.

PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Diffuse large B-cell non-Hodgkin's lymphoma

• Bulky stage II (bulk defined as any lesion ≥ 10 cm) or stage III or IV disease

• The following lymphoma types are excluded:

• Primary central nervous system lymphoma

• Transformed low-grade lymphoma (prior history of low-grade lymphoma or clear presence of low-grade lymphoma on histologic sections)

• Primary mediastinal B-cell lymphoma or testicular lymphoma (consolidative radiotherapy is usually indicated)

• Immunodeficiency-related lymphoma (i.e., after organ or bone marrow transplant)

• Measurable disease

• Patient must have at least one objective measurable disease site (i.e., measurable in at least 2 perpendicular parameters)

• Measurable disease in the liver is required if the liver is the only site of lymphoma involvement

• Abnormal positron emission tomography scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3

• For patients > 50 years of age, a normal ejection fraction by ECHO or MUGA is required within 6 weeks prior to registration

• Absolute neutrophil count ≥ 1,500/mm^3*

• Platelet count > 100,000/mm^3*

• Creatinine < 2.0 mg/dL*

• Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to liver involvement by lymphoma)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use an accepted and effective method of contraception

• No prior malignancy within the past 5 years unless it was in situ OR was treated with curative intent AND the patient has remained relapse-free

• HIV negative NOTE: *Unless abnormal due to lymphoma

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiation therapy for lymphoma

• No prior anthracyclines or platinum compounds used as systemic chemotherapy

• No prior radiation therapy to the mediastinum or to ≥ 25% of the bone marrow

• No concurrent pentostatin or trastuzumab (Herceptin®)

Trial Contact Information

Trial Lead Organizations/Sponsors

Eastern Cooperative Oncology Group

Lode J. Swinnen

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00274924
Information obtained from ClinicalTrials.gov on December 12, 2012

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