A Dose Range Finding Study of Lenalidomide in Non-5q Chromosome Deletion in Low and Intermediate Risk Myelodysplastic Syndrome (MDS) Patients
Revlimid® (Lenalidomide) is indicated for a type of blood cancer, myelodysplastic syndrome (MDS), at 10mg for a specific type of myelodysplastic syndrome with a genetic abnormality called "deletion 5q" in Low and Intermediate-1 (INT-1) patients (staging system according to International Prognostic Scoring System (IPSS)). The purpose of this Phase I/II study is to determine the optimal dose of Revlimid® (Lenalidomide) in MDS Low and MDS INT-1 patients without deletion 5q by slowly increasing the dose while monitoring blood counts for safety evaluation as well as observe other adverse events. Efficacy will also be observed for the phase II portion of the study.
Low to Intermediate-1 MDS
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients|
- Determine CR, PR, and rate of stable disease in MDS patients [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]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
- Safety with dose escalation [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Safety (type, frequency, severity, and relationship of adverse events to study treatment) with dose escalation.
|Study Start Date:||July 2008|
|Estimated Study Completion Date:||July 2013|
|Primary Completion Date:||January 2011 (Final data collection date for primary outcome measure)|
Lenalidomide will be given orally on day 1-21, followed by a 7day rest (28 day cycle). Cycles will be repeated every 28 days.
Dose Level Lenalidomide Schedule
Other Name: Revlimid
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.
|United States, Pennsylvania|
|Associates in Hematology-Oncology, PC|
|Chester, Pennsylvania, United States, 19130|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Emmanuel Besa, MD||Thomas Jefferson University|