Genes in Predicting Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab and Combination Chemotherapy
Overview[ - collapse ][ - ]
| 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. |
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| Condition | Lymphoma |
| Intervention | Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Prednisone Drug: Vincristine 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 |
| Phase | Phase 2 |
| Sponsor | University of Miami Sylvester Comprehensive Cancer Center |
| Responsible Party | University of Miami Sylvester Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier | NCT00450385 |
| First Received | March 20, 2007 |
| Last Updated | February 28, 2014 |
| Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | March 20, 2007 |
|---|---|
| Last Updated Date | February 28, 2014 |
| Start Date | February 2007 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures |
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| Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
| Brief Title | Genes in Predicting Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab and Combination Chemotherapy |
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| Official Title | Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP |
| Brief Summary | 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. |
| 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. |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Lymphoma |
| Intervention | Drug: Rituximab Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles Drug: Cyclophosphamide Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles Drug: Doxorubicin Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles Drug: 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 cycles Genetic: RNA-based gene array studies Diagnostic tumor tissue sample Genetic: Real time PCR gene expression studies Diagnostic tumor tissue sample Genetic: Tissue-array immunohistochemical studies Diagnostic tumor tissue sample Genetic: Immunoglobulin G Fc receptor genotypes determination Diagnostic tumor tissue sample |
| Study Arm (s) | Experimental: R-CHOP |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 213 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | December 2015 |
| Eligibility 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 |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00450385 |
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| Other Study ID Numbers | UMIAMI-20061138 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University of Miami Sylvester Comprehensive Cancer Center |
| Study Sponsor | University of Miami Sylvester Comprehensive Cancer Center |
| Collaborators | Not Provided |
| Investigators | Study Chair: Izidore S. Lossos, MD University of Miami Sylvester Comprehensive Cancer Center |
| Verification Date | February 2014 |
Locations[ + expand ][ + ]
| Stanford University | Stanford, California, United States, 94305 Contact: Ash A Alizadeh, MD/PhD | 650-725-0120 | arasha@stanford.eduPrincipal Investigator: Ash A Alizadeh, MD/PhD Recruiting |
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| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida, United States, 33136 Contact: University of Miami Sylvester Comprehensive Cancer Center Clin | 866-574-5124 | Sylvester@emergingmed.comRecruiting |