Genes in Predicting Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab and Combination Chemotherapy - Full Text View

Sponsored by:	Sylvester Cancer Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00450385

Purpose

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients respond to treatment.

PURPOSE: This phase II trial is studying how well genes and biomarkers predict outcome of patients with diffuse large B-cell lymphoma treated with rituximab and combination chemotherapy.

Condition	Intervention	Phase
Lymphoma	Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: rituximab Drug: vincristine sulfate Procedure: gene expression analysis Procedure: gene expression profiling Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: polymerase chain reaction Procedure: polymorphism analysis	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Cyclophosphamide Prednisone Vincristine sulfate Vincristine Rituximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP

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

Primary Outcome Measures:

Overall survival at 30 months [ Designated as safety issue: No ]
Biomarkers (immunoglobulin G Fc receptor genotypes, CD20 protein expression, and gene expression profiles) [ Designated as safety issue: No ]
Overall response [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to treatment failure [ Designated as safety issue: No ]
Response (complete response [CR], CR unconfirmed, partial response) [ Designated as safety issue: No ]

Estimated Enrollment:	213
Study Start Date:	February 2007
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine a list of genes and construct a survival prediction model(s) that will predict the overall survival at 30 months of patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone.
Determine the usefulness of biomarkers associated with the antitumor effects of rituximab (e.g., immunoglobulin G Fc receptor genotypes, CD20 protein expression, and gene expression profiles) in predicting overall survival of patients treated with this regimen.
Compare the ability of constructed survival models to predict survival of these patients.

Secondary

Determine the ability of the models and/or biomarkers associated with the antitumor effects of rituximab to predict 24-month time to treatment failure, defined as disease progression, death, or initiation of new treatment.
Determine the overall response rate (complete and partial response rate) at the end of study therapy.
Collect a series of fixed tissue samples with annotated clinical information and state of the art therapy for future studies.

OUTLINE: This is a prospective study.

Patients receive rituximab IV over 4-8 hours, cyclophosphamide IV over 2 hours, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with responding disease after completion of course 4 receive 4 additional courses of therapy.

Paraffin-embedded tissue blocks and immunohistochemical slides are collected at baseline for RNA-based gene array studies, real-time polymerase chain reaction gene expression studies, polymorphism analysis, tissue-array immunohistochemical studies, and immunoglobulin G Fc receptor genotypes determination.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 213 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of diffuse large B-cell lymphoma, meeting 1 of the following staging criteria:
- Limited stage I disease that is bulky (i.e., more than 10 cm) or with International Prognostic Index > 1
- Stage II-IV disease
CD20-positive disease
Paraffin-embedded tumor specimen must be available
No active CNS lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-3
WBC > 2,500/mm³
Absolute neutrophil count > 1,000/mm³ (unless due to disease in marrow)
Platelet count > 100,000/mm³ (unless due to disease in marrow)
Creatinine < 2.0 mg/dL
Bilirubin < 1.5 mg/dL (1.5-3.0 mg/dL if due to liver involvement by lymphoma)
AST and ALT < 3 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
LVEF > 45%
No HIV positivity
No other malignancy except for basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless the tumor was treated with curative intent ≥ 2 years ago and the patient continues to be free of evidence of recurrence)

PRIOR CONCURRENT THERAPY:

No prior chemotherapy, radiotherapy, or immunotherapy
- A prior short course (i.e., < 2 weeks) of corticosteroids allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00450385

Locations

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami	Recruiting
Miami, Florida, United States, 33136
Contact: University of Miami Sylvester Comprehensive Cancer Center Clin 866-574-5124 Sylvester@emergingmed.com

Sponsors and Collaborators

Sylvester Cancer Center

Investigators

Study Chair:

Izidore S. Lossos, MD

Sylvester Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	University of Miami Sylvester Comprehensive Cancer Center - Miami ( Izidore S. Lossos )
Study ID Numbers:	CDR0000537678, SCCC-2006069, SCCC-2007073, SCCC-1086970, SCCC-20061138
Study First Received:	March 20, 2007
Last Updated:	December 9, 2008
ClinicalTrials.gov Identifier:	NCT00450385
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma
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
stage I adult diffuse large cell lymphoma

Study placed in the following topic categories:

Prednisone
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Vincristine
Cyclophosphamide
Recurrence
Doxorubicin

Lymphoma, B-Cell
Lymphoma, large-cell
Lymphatic Diseases
B-cell lymphomas
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antimitotic Agents
Antibiotics, Antineoplastic

Hormones
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009