Everolimus, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Untreated Diffuse Large B-Cell Lymphoma
RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer cells 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Giving everolimus together with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and the best dose of everolimus when given together with rituximab and combination chemotherapy in treating patients with newly diagnosed untreated diffuse large B-cell lymphoma.
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I and Feasibility Study of Everolimus (RAD001) Plus R-CHOP for New Untreated Diffuse Large B-Cell Lymphoma (DLBCL)|
- MTD of everolimus in combination with R-CHOP [ Time Frame: Up to 15 months post registration to Phase I portion of the study ]
- Adverse events profile [ Time Frame: Up to 15 months post registration to Phase I portion of the study ]
- Toxicity profile [ Time Frame: Up to 15 months post registration to Phase I portion of the study ]
- Proportion of patients who have a significant toxicity [ Time Frame: Up to 2.5 years post registration to Feasibility portion of the study ]
- Rate of EFS [ Time Frame: Up to 5 years post treatment of the feasibility portion of the study ]
- Overall response rate, CR rate, overall survival, PFS, and duration of response [ Time Frame: Up to 5 years post treatment of the feasibility portion of the study ]
|Study Start Date:||March 2012|
|Estimated Primary Completion Date:||February 2020 (Final data collection date for primary outcome measure)|
Experimental: everolimus and RCHOP
Patients registered to the study will receive an assigned dose of everolimus by mouth and RCHOP for a maximum of six cycles. Each cycle is a total of 21 days. RCHOP consists of 375 mg/m2 IV rituximab, 750 mg/m2 IV cyclophosphamide, 50 mg/m2 IV doxorubicin, 1.4 mg/m2 IV vincristine and 100 mg/m2 by mouth QD prednisone. The study includes a Phase I component to determine the maximum tolerated dose of everolimus and the second component determines the feasibility of therapy administered to lymphoma patients.
IVDrug: doxorubicin hydrochloride
PODrug: vincristine sulfate
- To establish the maximum-tolerated dose (MTD) of everolimus in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone) chemotherapy.
- To assess the feasibility of everolimus in combination with standard R-CHOP chemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma.
- To describe the toxicities associated with everolimus in combination with R-CHOP chemotherapy.
- To further describe the toxicities associated with everolimus in combination with R-CHOP chemotherapy.
- To assess the rate of event-free survival (EFS) at 12 months for diffuse large B-cell lymphoma patients treated with everolimus in combination with R-CHOP chemotherapy.
- To evaluate overall response rate, complete response rate, duration of response, EFS, overall survival, and progression-free survival for patients treated with everolimus in combination with R-CHOP chemotherapy.
- To profile gene expression using immunohistochemistry and categorize patients as germinal-center B-cell-like (GBC) vs activated B-cell-like (ABC) vs unclassified lymphoma subtype. (exploratory)
- To determine whether previously identified predictive markers in large cell lymphoma remain valid with the addition of everolimus to R-CHOP chemotherapy. (exploratory)
OUTLINE: This is a multicenter, dose-escalation study of everolimus followed by a feasability expanded-cohort study.
Patients receive everolimus orally (PO) once daily (QD) on days 1-10 or 1-14; rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV over 15-60 minutes, and vincristine sulfate IV on day 1; and prednisone PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Tumor biopsies are collected for laboratory studies and patients may undergo blood and needle biopsy sample collection for correlative studies.
After completion of study treatment, patients are followed up every 3-6 months for up to 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01334502
|United States, Minnesota|
|Mayo Clinic Cancer Center|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Patrick Johnston, MD, PhD||Mayo Clinic|