A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia.
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.
['Griffiths|Elizabeth A|EA|', 'Brady|William E|WE|', 'Tan|Wei|W|', 'Vigil|Carlos E|CE|', 'Thompson|James E|JE|', 'Ford|Laurie A|LA|', 'Dickey|Noelle M|NM|', 'L Bashaw|Heather|H|', 'Sperrazza|Jill|J|', 'Wetzler|Meir|M|', 'Wang|Eunice S|ES|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D003561:Cytarabine D018572:Disease-Free Survival D005260:Female D006801:Humans D000077269:Lenalidomide D015470:Leukemia, Myeloid, Acute D008297:Male D008875:Middle Aged D015996:Survival Rate D013792:Thalidomide
Phase I Cytarabine Lenalidomide Acute myeloid leukemia Clinical trial Relapse/refractory AML