Lymphocytic Leukemia Clinical Trial
Official title:
Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Everolimus (RAD001) and Alemtuzumab: A Phase I/II Study
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).
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. ;
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