Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with everolimus (RAD001) and alemtuzumab: a Phase I/II study

Clive S. Zent, Deborah A. Bowen, Michael J. Conte, Betsy R. LaPlant, Timothy G. Call

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - Dec 23 2015

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
Maximum Tolerated Dose
Therapeutics
Sequence Deletion
Lymphoid Tissue
Sirolimus
B-Lymphocytes
Everolimus
alemtuzumab
Clinical Trials

Keywords

  • alemtuzumab
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma
  • everolimus
  • mTOR TORC1 inhibitor
  • relapsed/ refractory CLL

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with everolimus (RAD001) and alemtuzumab : a Phase I/II study. / Zent, Clive S.; Bowen, Deborah A.; Conte, Michael J.; LaPlant, Betsy R.; Call, Timothy G.

In: Leukemia and Lymphoma, 23.12.2015, p. 1-7.

Research output: Contribution to journalArticle

Zent, Clive S. ; Bowen, Deborah A. ; Conte, Michael J. ; LaPlant, Betsy R. ; Call, Timothy G. / Treatment of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma with everolimus (RAD001) and alemtuzumab : a Phase I/II study. In: Leukemia and Lymphoma. 2015 ; pp. 1-7.
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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.",
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