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

NCT00121199 | Completed Phase 2 Results

• 3 other identifiers: NCI-2012-03062S0515U10CA032102
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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.

Conditions

Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival at 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

  0-1 year

• Progression-free Survival at 2 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

  0-2 years

Secondary Outcomes (2)

• 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

Study Arms (1)

Treatment (CHOP, rituximab, bevacizumab)

EXPERIMENTAL

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.

Biological: rituximab; Biological: bevacizumab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Other: laboratory biomarker analysis

Interventions

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (CHOP, rituximab, bevacizumab)

bevacizumab BIOLOGICAL

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Treatment (CHOP, rituximab, bevacizumab)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (CHOP, rituximab, bevacizumab)

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Treatment (CHOP, rituximab, bevacizumab)

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Treatment (CHOP, rituximab, bevacizumab)

prednisone DRUG

Given PO

Also known as: DeCortin, Deltra

Treatment (CHOP, rituximab, bevacizumab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (CHOP, rituximab, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Serum LDH must be measured within 28 days prior to registration
• Patients must have a cardiac ejection fraction \>= 45% by MUGA scan or a 2-d ECHO with no significant abnormalities within 42 days prior to registration
• Absolute neutrophil count \> 1,000/mcL obtained within 28 days prior to registration
• Platelet count \> 100,000/mcL obtained within 28 days prior to registration
• Serum creatinine \< 2 x the institutional upper limit of normal within 28 days prior to registration

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

SWOG

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• 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. doi: 10.1182/blood-2012-04-423079. Epub 2012 Jun 25.

  PMID: 22734071 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Bevacizumab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Study Statistician
• Organization: SWOG Statistical Center

206-667-4623

Study Officials

• Alison Stopeck

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2005
• First Posted: July 21, 2005
• Study Start: June 1, 2005
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: May 21, 2014
• Results First Posted: December 19, 2012

Record last verified: 2012-12

Locations

US (1)