S0515 Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma
RATIONALE: 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.
PURPOSE: 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.
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab Plus Bevacizumab for Advanced Stage Diffuse Large B-Cell NHL|
- Progression-free Survival at 1 Year [ Time Frame: 0-1 year ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
- Objective Response (Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR)) [ Time Frame: 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. ] [ Designated as safety issue: No ]Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
- Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events after every cycle (1 cycle = 21 days) of protocol treatment ] [ Designated as safety issue: Yes ]Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
|Study Start Date:||June 2005|
|Primary Completion Date:||December 2010 (Final data collection date for primary outcome measure)|
Experimental: combination chemo with rituximab and bevacizumab
combination chemo with rituximab and bevacizumab
|Biological: bevacizumab Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate|
- Determine the 1-year progression-free survival rate in patients with bulky stage II or stage III or IV diffuse large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab in combination with bevacizumab.
- Determine the response rate (complete response, complete unconfirmed response, and partial response) and 2-year progression-free survival of patients treated with this regimen.
- Determine the toxic effects of this regimen in these patients.
- Correlate angiogenic biomarkers with outcome in patients treated with this regimen.
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.
PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 18 months.