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Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is ongoing, but not recruiting participants.
Information provided by:
Mayo Clinic Identifier:
First received: July 6, 2009
Last updated: December 4, 2013
Last verified: December 2013

July 6, 2009
December 4, 2013
July 2009
January 2014   (final data collection date for primary outcome measure)
Clinical response (complete or partial remission) (phase II) [ Time Frame: After 2 courses of treatment ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00935792 on Archive Site
  • 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 ]
  • Survival time [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to subsequent therapy [ Designated as safety issue: No ]
  • Number of complete responses [ Designated as safety issue: No ]
  • Serial measurements of clinical status and lymphocyte counts [ Designated as safety issue: No ]
  • IgVH gene mutation, CD38, CD49d, ZAP-70, and FISH status [ Time Frame: At baseline ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
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.

Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphocytic Leukemia
  • Drug: alemtuzumab
    Given subcutaneously
    Other Names:
    • anti-CD52 monoclonal antibody
    • MoAb CD52
    • Monoclonal Antibody Campath-1H
    • Campath-1H
    • Monoclonal Antibody CD52
    • Campath
  • Drug: everolimus
    Given orally
    Other Names:
    • Certican
    • RAD001
    • 42-O-(2-Hydroxy)ethyl Rapamycin
Experimental: Arm I
Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
  • Drug: alemtuzumab
  • Drug: everolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
Not Provided
January 2014   (final data collection date for primary outcome measure)


  • Diagnosis of CLL manifested by minimum threshold peripheral lymphocyte count of > 5 x 10^9/L (CLL variant) OR palpable adenopathy >= 1cm or clinically palpable splenomegaly (SLL variant); AND immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) which are monoclonal (by light chain exclusion)
  • CLL will be diagnosed if these cells have >= 3 of the following characteristics: CD5+, CD23+, dim surface light chain expression, dim surface CD20 expression, AND FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression to exclude mantle cell lymphoma Previous treatment for CLL Progressive disease: symptomatic CLL (weight loss>10% within 6 months, extreme fatigue, fevers>38.5 C, drenching night sweats without evidence of infection) OR evidence of progressive bone marrow failure (hemoglobin<11g/dL, platelet count<100 x 10^9/L) OR massive (>6 cm below left costal margin) or progressive palpable splenomegaly OR massive (>10 cm) or measurable and progressive lymphadenopathy
  • Please contact study investigator and/or consult protocol document for specific details on laboratory criteria CD52 expression by CLL cells Willing to provide mandatory biospecimen samples for research studies as required by the protocol Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only Willingness to return to the enrolling institution for follow-up
  • ECOG Performance Status (PS) 0, 1, or 2--Exceptions: Grade 3 allowed if caused by CLL and not other co-morbidities Provide informed written consent Life expectancy >= 3 months


  • Any of the following comorbid conditions: NYHA class III-IV heart disease, recent myocardial infarction (< 6 months prior to registration), uncontrolled infection, infection with the human immunodeficiency virus (HIV/AIDS), serological evidence of active hepatitis B infection (HBsAg or HBeAg positive) or positive hepatitis C serology, as further severe immunosuppression with this regimen may occur
  • Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia Other active primary malignancy requiring treatment or that limits survival to =< 2 years Any major surgery =< 4 weeks prior to registration Concurrent investigational drug therapy Any of the following: pregnant women,nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, abstinence, etc.)
  • Concomitant use of the following CYP3A4 strong inhibitors: Clarithromycin, Nefazodone, Telithromycin, Aprepitant, Indinavir, Nelfinavir, Diltiazem, Borisonazole, Itrazonazole, Ritonavir, Erythromycin, Ketoconazole, Saquinavir, Fluconazole (may be used if drug levels can be monitored)
  • Patients with any known bleeding diathesis (any congenital bleeding disorder that affects platelet function and/or coagulation including von Willebrand's Disease)
  • Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air Receiving anticoagulant therapy
18 Years and older
Contact information is only displayed when the study is recruiting subjects
United States
MC088C, MC088C, NCI-2009-00935, 08-008775
Clive S. Zent, M.D., Mayo Clinic Cancer Center
Mayo Clinic
Not Provided
Study Chair: Clive S. Zent, M.D. Mayo Clinic
Principal Investigator: Jose F. Leis, M.D. Mayo Clinic in Arizona
Mayo Clinic
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP