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
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: bevacizumab
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: prednisone
Drug: vincristine sulfate
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 73
Study Start Date: June 2005
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00121199

  Show 159 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Alison T. Stopeck, MD University of Arizona
Study Chair: Thomas P. Miller, MD University of Arizona
  More Information

Additional Information:
No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00121199     History of Changes
Other Study ID Numbers: NCI-2012-03062, U10CA032102, S0515, CDR0000434636
Study First Received: July 19, 2005
Results First Received: October 30, 2012
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Bevacizumab
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on April 16, 2014