Phase II Trial of Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab Plus Bevacizumab for Advanced Stage Diffuse Large B-Cell NHL
Overview
- Phase
- Phase 2
- Intervention
- rituximab
- Conditions
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- Progression-free Survival at 1 Year
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This phase II trial is studying how well giving combination chemotherapy together with rituximab and bevacizumab works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma. 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 more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as rituximab and bevacizumab, 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. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving combination chemotherapy together with monoclonal antibodies may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVES: I. To estimate the 1-year progression-free survival rate in patients with advanced stage diffuse large B-cell NHL treated with CHOP - rituximab - bevacizumab. II. To estimate the response rate (complete, complete unconfirmed, and partial) and 2-year progression-free survival of this regimen in patients with advanced stage diffuse large B-cell NHL. III. To evaluate the toxicities associated with this regimen. IV. To correlate angiogenic biomarkers with patient outcome. OUTLINE: This is a multicenter study. Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at least every 6 months for 2 years and then annually for 3 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; a report providing confirmation of CD20 expression must be submitted
- •Pathology Review: Adequate sections from the original diagnostic specimen must be available for submission for review by the SWOG Lymphoma Pathology Laboratory; 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
- •Specimens for analysis of angiogenic markers must be submitted to the University of Arizona
- •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 nonmeasurable disease assessed within 42 days prior to registration
- •Patients must have a unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
- •Patients must have a CT scan of the chest/abdomen and 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 may not have a previous diagnosis of indolent lymphoma (histologic transformation or mixed histologies with an indolent or nodular component are ineligible)
- •Patients must not have received prior chemotherapy, radiation, or antibody-based therapy for lymphoma
- •Patients must have a Zubrod performance status of 0 - 2
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: rituximab
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: bevacizumab
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: cyclophosphamide
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: doxorubicin hydrochloride
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: vincristine sulfate
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: prednisone
Treatment (CHOP, rituximab, bevacizumab)
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Progression-free Survival at 1 Year
Time Frame: 0-1 year
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Progression-free Survival at 2 Year
Time Frame: 0-2 years
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Secondary Outcomes
- Objective Response (Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR))(After Cycle 4 (Day 64) but prior to Cycle 5 (Day 85) and after Cycle 8 (Day 181). After completion of protocol treatment, every 6 months for 2 years, then annually for a maximum of five years.)
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug(Patients were assessed for adverse events after every cycle (1 cycle = 21 days) of protocol treatment)