title: Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with everolimus (RAD001) and alemtuzumab: a Phase I/II study.
abstract: Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL), and especially those with purine analogue refractory disease or TP53 deletion/mutation, had a poor prognosis prior to the introduction of therapy targeting B cell receptor signaling. The mammalian target of rapamycin (mTOR) inhibitor everolimus has biological activity in CLL and can mobilize CLL cells from the lymphoid tissues into the circulation. In this clinical trial we determined the maximum tolerated dose (MTD) of everolimus together with eight weeks of standard dose subcutaneous alemtuzumab (Phase I) and then evaluated the tolerability and efficacy of therapy of relapsed/refractory CLL with the combination of everolimus and alemtuzumab (Phase II). The maximum tolerated dose of oral everolimus was 2.5 mg three times/week. Therapy with everolimus and alemtuzumab was tolerable, but not sufficiently efficacious (33% partial responses, no complete responses) to recommend further development of the regimen.
authors.affiliation: a Division of Hematology , Mayo Clinic , Rochester, NY , USA ;
authors.forename: Clive S
authors.initials: CS
authors.lastname: Zent
authors.affiliation: a Division of Hematology , Mayo Clinic , Rochester, NY , USA ;
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Bowen
authors.affiliation: a Division of Hematology , Mayo Clinic , Rochester, NY , USA ;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Conte
authors.affiliation: b Department of Health Sciences Research , Mayo Clinic , Rochester, NY , USA.
authors.forename: Betsy R
authors.initials: BR
authors.lastname: LaPlant
authors.affiliation: a Division of Hematology , Mayo Clinic , Rochester, NY , USA ;
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D019233:Retreatment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000074323:Alemtuzumab; D000068338:Everolimus
keywords: Chronic lymphocytic leukemia/small lymphocytic lymphoma; alemtuzumab; everolimus; mTOR TORC1 inhibitor; relapsed/ refractory CLL