title: A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia.
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/m(2)/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25mg 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.
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States. Electronic address: elizabeth.griffiths@roswellpark.org.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Griffiths
authors.affiliation: Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: William E
authors.initials: WE
authors.lastname: Brady
authors.affiliation: Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Vigil
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Thompson
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States; Clinical Research Services, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Ford
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States; Clinical Research Services, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Noelle M
authors.initials: NM
authors.lastname: Dickey
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States; Clinical Research Services, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: L Bashaw
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Jill
authors.initials: J
authors.lastname: Sperrazza
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263, United States.
authors.forename: Eunice S
authors.initials: ES
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D003561:Cytarabine; D013792:Thalidomide; D000077269:Lenalidomide
keywords: Acute myeloid leukemia; Clinical trial; Cytarabine; Lenalidomide; Phase I; Relapse/refractory AML