Clinical Trial: A Dose Range Finding Study of Lenalidomide in Non-5q Chromosome Deletion in Low and Intermediate Risk Myelodysplastic Syndrome (MDS) Patients

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients

Brief Summary: 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.

Detailed Summary:

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.


Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Current Primary Outcome: Determine CR, PR, and Rate of Stable Disease in MDS Patients [ Time Frame: 2 years ]

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


Original Primary Outcome: 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 [ Time Frame: 2 years ]

Current Secondary Outcome: Safety With Dose Escalation [ Time Frame: 2 years ]

Safety (type, frequency, severity, and relationship of adverse events to study treatment) with dose escalation.


Original Secondary Outcome: Safety (type, frequency, severity, and relationship of adverse events to study treatment) with dose escalation. [ Time Frame: 2 years ]

Information By: Thomas Jefferson University

Dates:
Date Received: June 13, 2008
Date Started: July 2008
Date Completion:
Last Updated: October 19, 2016
Last Verified: October 2016