Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the signaling molecules needed for cell growth. Monoclonal antibodies, such as alemtuzumab, can bind to and kill malignant lymphocytes.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with alemtuzumab and will see how well they work in treating patients with recurrent chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Everolimus (RAD001) and Alemtuzumab: A Phase I/II Study|
- Clinical response (complete or partial remission) (phase II) [ Time Frame: After 2 courses of treatment ] [ Designated as safety issue: No ]
- Survival time [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Duration of response [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Time to subsequent therapy [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Number of complete responses [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- Serial measurements of clinical status and lymphocyte counts [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
- IgVH gene mutation, CD38, CD49d, ZAP-70, and FISH status [ Time Frame: At baseline ] [ Designated as safety issue: No ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: up to 5 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2009|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Other Names:Drug: everolimus
PRIMARY OBJECTIVES: I. Test the safety and tolerability of the combination of everolimus and alemtuzumab. (Phase I) II. Determine the maximum tolerated dose of everolimus in this combination. (Phase I) III. Assess the rate of overall responses in patients with relapsed/refractory CLL to treatment with the maximum tolerated dose of everolimus together with a standard dose of alemtuzumab using conventional NCI-WG 1996 response criteria. (Phase II) IV. To assess the complete responses to this combination regimen using conventional NCI-WG 1996 criteria and an expanded definition of response, including CT scans of chest-abdomen-pelvis, immunohistochemical analysis for residual disease in the bone marrow, and sensitive flow cytometry for minimal residual disease in patients in complete clinical remission. V. To monitor and assess toxicity of this regimen. SECONDARY OBJECTIVES: I. To determine the overall and progression-free survival, duration of response, and time to next treatment. II. To assess the correlation between the individual prognostic markers (17p-, p53 gene mutations, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+, CD49d, B2 microglobulin) and clinical outcome. III. Serial measurement of clinical status and lymphocyte counts to test the rate of reduction in CLL tumor burden. TERTIARY OBJECTIVES: I. Determine the effect of everolimus on the sensitivity of CLL cells to alemtuzumab CDC and ADCC. II. Determine the effect of everolimus on the CLL cell-stroma interaction. III. Detail the in vivo effect of the everolimus-alemtuzumab regimen on critical aspects of the immune system in CLL. OUTLINE: This is a phase I, dose escalation study of everolimus followed by a phase II study. Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 7 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00935792
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Clive S. Zent, M.D.||Mayo Clinic|
|Principal Investigator:||Jose F. Leis, M.D.||Mayo Clinic in Arizona|