S0515 Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00121199
First received: July 19, 2005
Last updated: January 4, 2013
Last verified: January 2013

July 19, 2005
January 4, 2013
June 2005
December 2010   (final data collection date for primary outcome measure)
  • 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
Not Provided
Complete list of historical versions of study NCT00121199 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
S0515 Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma
Phase II Trial of Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab Plus Bevacizumab for Advanced Stage Diffuse Large B-Cell NHL

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.

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Biological: bevacizumab
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: prednisone
  • Drug: vincristine sulfate
Experimental: combination chemo with rituximab and bevacizumab
combination chemo with rituximab and bevacizumab
Interventions:
  • Biological: bevacizumab
  • Biological: rituximab
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: prednisone
  • Drug: vincristine sulfate
Stopeck AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP. A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012 Aug 9;120(6):1210-7. Epub 2012 Jun 25.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
73
Not Provided
December 2010   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically confirmed* diffuse large B-cell lymphoma, meeting 1 of the following stage criteria:

    • Bulky stage II
    • Stage III
    • Stage IV NOTE: *Adequate sections from the original diagnostic specimen must be available; needle aspiration or cytology are not considered adequate
  • Bidimensionally measurable disease
  • CD20-positive disease
  • No prior indolent lymphoma, including histologic transformation or mixed histology with an indolent or nodular component
  • No clinical evidence of CNS involvement by lymphoma

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3
  • No bleeding diathesis or coagulopathy

Hepatic

  • Not specified

Renal

  • Creatinine < 2 times upper limit of normal
  • No proteinuria ≥ +1 by dipstick or urinalysis OR
  • Urine protein:creatinine ratio < 1.0 OR
  • Urine protein < 1 g by 24-hour urine collection

Cardiovascular

  • No uncontrolled hypertension
  • No myocardial infarction within the past 6 months
  • No unstable angina within the past 6 months
  • No stroke within the past 6 months
  • No arterial thrombosis within the past 6 months
  • No clinically significant peripheral vascular disease
  • Ejection fraction ≥ 45% by MUGA or 2-dimensional echocardiogram (2-D ECHO)
  • No significant cardiac abnormality by MUGA or 2-D ECHO

Pulmonary

  • No requirement for continuous supplemental oxygen

Gastrointestinal

  • No abdominal fistula within the past 6 months
  • No gastrointestinal perforation within the past 6 months
  • No intra-abdominal abscess within the past 6 months

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 months after completion of study therapy
  • No known HIV positivity
  • No history of hypersensitivity reaction to products containing polysorbate 20 (Tween 20), Chinese hamster ovary cell products, or recombinant human antibodies
  • No traumatic injury within the past 28 days
  • No serious or non-healing wound, ulcer, or bone fracture
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior antibody-based therapy for lymphoma

Chemotherapy

  • No prior chemotherapy for lymphoma

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy for lymphoma

Surgery

  • More than 28 days since prior and no concurrent major surgery
  • No prior solid organ transplantation

Other

  • Concurrent full-dose anticoagulants allowed for treatment of venous thrombosis provided the following criteria are met:

    • INR in range (i.e., 2-3)
    • Patient is on a stable dose of warfarin or low molecular weight heparin
    • No bleeding or pathological condition that would confer a high risk of bleeding (e.g., tumor involving major vessels or known varices)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00121199
NCI-2012-03062, U10CA032102, S0515, CDR0000434636
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Study Chair: Alison T. Stopeck, MD University of Arizona
Study Chair: Thomas P. Miller, MD University of Arizona
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP