Efficacy and Safety of Lenalidomide in Combination With Cyclosporine A in Patients With Myelodysplastic Syndromes
Status:
Terminated
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
Lenalidomide has shown significant efficacy in the treatment of anemia associated with both
5q- and non 5q- MDS patients. The mechanism(s) of action of lenalidomide in MDS is still to
be determined, but given the differences in response rates seen, it is probable that the
mechanism is different for patients with 5q- disease compared to non 5q- patients. T-cell
mediated activation of intramedullary apoptosis in patients with early MDS leading to
impaired hematopoiesis has been well described. Immunomodulation with agents such as ATG,
cyclosporine and thalidomide have demonstrated clear activity in some patients with MDS.
Lenalidomide, among its many effects, is a potent immunomodulator, which may contribute to
its ability to improve red blood cell counts in patients with MDS. It is possible that this
effect could be augmented with the addition of cyclosporine A (CSA), in a similar manner to
CSA effects in patients with other bone marrow failure syndromes such as aplastic anemia.
Subjects will be treated with lenalidomide 10 mg PO daily days 1-28 of a 28-day cycle.
Cyclosporine A will be started on day 1 of cycle 2 (day 29) at a dose of 5 mg/kg per day
given orally in 2 divided doses. Cyclosporine A levels will be assessed weekly and doses will
be adjusted to maintain a serum trough level between 100-450 mg/ml. Patients will continue on
therapy for minimum of 16 weeks unless toxicity occurs which precludes continuation on
therapy, disease progression and/or patient withdrawal of consent. Patients not achieving
response after completing 16 weeks of therapy will discontinue treatment. Patients achieving
response will continue therapy until disease progression, unacceptable toxicity or loss of
response.