Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab, or Rituximab and G3139 Phosphorothioate Oligonucleotide (BCL-2 Antisense - NSC-683428) Therapy for Young Patients (< Age 60) With Advanced Stage Diffuse Large B-Cell NHL of Low and Low-Intermediate IPI Risk
Overview
- Phase
- Phase 2
- Intervention
- rituximab
- Conditions
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 160
- Locations
- 1
- Primary Endpoint
- 1 year PFS
- Status
- Terminated
- Last Updated
- 13 years ago
Overview
Brief Summary
This randomized phase II trial is studying rituximab and combination chemotherapy to see how well they work compared to oblimersen, rituximab, and combination chemotherapy in treating patients with advanced diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of anticancer drugs by making cancer cells more sensitive to the drugs. Combining rituximab and combination chemotherapy with oblimersen may kill more cancer cells
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the 1-year progression-free survival probability rate in younger patients with low and low-intermediate IPI risk advanced stage diffuse large B-cell NHL treated with 8-cycles of CHOP-rituximab. (The CHOP-rituximab arm of this study was permanently closed, effective 10/15/04.) II. To estimate the 1-year progression-free survival probability rate in younger patients with low and low-intermediate IPI risk advanced stage diffuse large B-cell NHL treated with 8 cycles of CHOP-rituximab-G3139. III. To evaluate response (complete, complete unconfirmed, and partial) and toxicity for these regimens in this patient population. (The CHOP-rituximab arm of this study was permanently closed, effective 10/15/04.) IV. To estimate the 1-year progression-free survival and response rate in the subset of patients overexpressing bcl-2 protein. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age-adjusted International Prognostic Index (0 vs 1). Patients are randomized to 1 of 2 treatment arms. (Arm I closed to accrual as of 9/21/04.) ARM I (closed to accrual as of 9/21/04): Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5. ARM II: Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10. In both arms, treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for up to 5 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All patients must have previously untreated stage III, IV, or bulky stage II diffuse large B-cell non-Hodgkin's lymphoma which is positive for CD20
- •Adequate sections from the original diagnostic specimen must be available for submission for review; an adequate biopsy requires sufficient tissue to establish the architecture and a REAL or WHO histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies MAY be adequate; whereas, needle aspirations or cytologies are not adequate
- •Patients may also be registered to SWOG-8947 and SWOG-8819
- •Patients must have an age-adjusted International Prognostic Index score of 0 or 1
- •All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
- •Patients must have a unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
- •Patients must have a CT scan of the chest and abdomen/pelvis performed within 28 days prior to registration
- •Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration
- •Patients must not have a previous diagnosis of indolent lymphoma (histologic transformation are ineligible); as patients with nodal diffuse large ell lymphoma may have bone marrow involvement with small lymphocytes, such patients are eligible
- •Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (closed to accrual as of 9/21/04)
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Intervention: rituximab
Arm I (closed to accrual as of 9/21/04)
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Intervention: cyclophosphamide
Arm I (closed to accrual as of 9/21/04)
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Intervention: doxorubicin hydrochloride
Arm I (closed to accrual as of 9/21/04)
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Intervention: vincristine sulfate
Arm I (closed to accrual as of 9/21/04)
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Intervention: prednisone
Arm I (closed to accrual as of 9/21/04)
Patients receive rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 1 and oral prednisone on days 1-5.
Intervention: laboratory biomarker analysis
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: oblimersen sodium
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: rituximab
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: cyclophosphamide
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: doxorubicin hydrochloride
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: vincristine sulfate
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: prednisone
Arm II
Patients receive oblimersen IV continuously on days 1-7; rituximab IV over 6 hours, cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-20 minutes, and vincristine IV over 5-15 minutes on day 5; and oral prednisone on days 5-10.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
1 year PFS
Time Frame: At 1 year
Secondary Outcomes
- Overall survival(Up to 7 years)
- Response(Up to 7 years)
- 1-year PFS in patients who are bcl2+(At 1 year)
- Overall survival in patients who are bcl2+(Up to 7 years)
- Response in patients who are bcl2+(Up to 7 years)