A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia

Elizabeth A. Griffiths*, William E. Brady, Wei Tan, Carlos E. Vigil, James E. Thompson, Laurie A. Ford, Noelle M. Dickey, Heather L. Bashaw, Jill Sperrazza, Meir Wetzler, Eunice S. Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m2/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10 mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25 mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.

Original languageEnglish (US)
Pages (from-to)44-48
Number of pages5
JournalLeukemia Research
Volume43
DOIs
StatePublished - Apr 1 2016

Funding

The authors would like to thank the patients who participated in this and all clinical trials, without whom no improvement in therapy would be possible. This study was an investigator initiated clinical trial sponsored by Celgene, Inc . The study investigators were supported partially by grants from the National Cancer Institute Grant CA16056 (EAG, MW), the Szefel Foundation (MW), the Leonard S. LoVullo Endowment for Leukemia Research (MW), the Nancy C. Cully Endowment for Leukemia Research (MW), the Babcock Family Endowment (MW), the Heidi Leukemia Research Fund (MW), and the Roswell Park Alliance Foundation (EAG). The study used shared resources supported by RPCI’s Cancer Center Support Grant from the NCI (P30CA016056). EAG discloses honoraria from Celgene Inc. and Alexion Pharmaceuticals, advisory board contributions to Ariad Pharmaceuticals and research funding and honoraria from Astex Pharmaceuticals . MW received honoraria and research funding from Teva Pharmacueticals .

Keywords

  • Acute myeloid leukemia
  • Clinical trial
  • Cytarabine
  • Lenalidomide
  • Phase I
  • Relapse/refractory AML

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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