Genes in Predicting Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab and Combination Chemotherapy
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.
Genetic: RNA-based gene array studies
Genetic: Real time PCR gene expression studies
Genetic: Tissue-array immunohistochemical studies
Genetic: Immunoglobulin G Fc receptor genotypes determination
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP|
- Overall survival at 30 months [ Time Frame: At study completion ] [ Designated as safety issue: No ]
- Biomarkers (immunoglobulin G Fc receptor genotypes, CD20 protein expression, and gene expression profiles) [ Time Frame: At study completion ] [ Designated as safety issue: No ]
- Overall response [ Time Frame: At study completion ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: At study completion ] [ Designated as safety issue: No ]
- Time to treatment failure [ Time Frame: At study completion ] [ Designated as safety issue: No ]
- Response (complete response [CR], CR unconfirmed, partial response) [ Time Frame: At study completion ] [ Designated as safety issue: No ]
|Study Start Date:||February 2007|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Rituximab 375 mg/m2 on day 1 for 6 to 8 cyclesDrug: Cyclophosphamide
Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cyclesDrug: Doxorubicin
Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cyclesDrug: Prednisone
Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.Drug: Vincristine
Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cyclesGenetic: RNA-based gene array studies
Diagnostic tumor tissue sampleGenetic: Real time PCR gene expression studies
Diagnostic tumor tissue sampleGenetic: Tissue-array immunohistochemical studies
Diagnostic tumor tissue sampleGenetic: Immunoglobulin G Fc receptor genotypes determination
Diagnostic tumor tissue sample
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00450385
|United States, California|
|Stanford, California, United States, 94305|
|Contact: Ash A Alizadeh, MD/PhD 650-725-0120 email@example.com|
|Principal Investigator: Ash A Alizadeh, MD/PhD|
|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|
|Study Chair:||Izidore S. Lossos, MD||University of Miami Sylvester Comprehensive Cancer Center|