A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients
There are little options for non deletion 5q Low and INT-1 patients. This study aims to
find an early clinical signal for higher activity and better response with lenalidomide in
patients with non deletion 5q Low and INT-1 MDS patients. Lenalidomide is an
immunomodulatory agent. Thalidomide, the parent compound, has both immunomodulatory and
anti-angiogenic properties which could confer anti-tumor and anti-metastatic efforts.
Lenalidomide has been demonstrated to possess anti-angiogenic activity through inhibition of
basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and tumor
necrosis factor-alpha (TNF-alpha) induced endothelial cell migration (movement of cells in
preparation to form new abnormal blood vessels for cancer cells), due at least in part to
inhibition of Akt phosphorylation response to bFGF.
In addition, lenalidomide has a variety of immunomodulatory effects. Lenalidomide stimulates
T cell proliferation, and the production of interleukin-2 (IL-2), IL-10 and interferon-gamma
(IFN-gamma), inhibits IL-1 beta and IL-6 and modulated IL-12 production.
Although the exact anti-tumor mechanism of action of lenalidomide is unknown, a number of
mechanisms are postulated for the activity of Lenalidomide in MDS.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine CR, PR, and rate of stable disease in MDS patients
Determine CR, PR, and rate of stable disease in MDS patients, IPSS Score LOW or INT-1 who do not have the 5q- cytogenetic abnormality according to the IWG criteria for response in >10mg doses of lenalidomide
Emmanuel Besa, MD
Thomas Jefferson University
United States: Food and Drug Administration
|Thomas Jefferson University||Philadelphia, Pennsylvania 19107-6541|
|Associates in Hematology-Oncology, PC||Chester, Pennsylvania 19130|