Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Condition: Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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).
    

Detailed description: 
      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.
    

Intervention name(s): alemtuzumab; everolimus
Intervention type(s): Drug; Drug
Intervention description(s): Given subcutaneously; Given orally
Other intervention name(s): anti-CD52 monoclonal antibody; MoAb CD52; Monoclonal Antibody Campath-1H; Campath-1H; Monoclonal Antibody CD52; Campath; Certican; RAD001; 42-O-(2-Hydroxy)ethyl Rapamycin
Intervention MeSH terms: Antineoplastic Agents, Immunological; Alemtuzumab; Everolimus; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hematopoietic cancer; lymphoid cancer