Phase I Study of an Immunomodulatory Thalidomide Analog, CC-4047, in Relapsed or Refractory Multiple Myeloma

• DOI: 10.1200/jco.2004.10.052
• Publication Date: 2004-07-13T00:18:28Z
• Authors: S.A. Schey; P. Fields; J.B. Bartlett; I.A. Clarke; G. Ashan; R.D. Knight; M. Streetly; A.G. Dalgleish
• Keywords: Refractory (planetary science); Concomitant; Regimen

To assess the safety, efficacy, and immunomodulatory effects of CC-4047 (Actimid; Celgene, San Diego, CA) in patients with relapsed or refractory myeloma.Twenty-four were treated a dose-escalating regimen oral CC-4047. Clinical responses adverse identified, peripheral T-cell subsets, serum cytokines, proangiogenic factors evaluated.CC-4047 was tolerated no serious nonhematologic events. All eligible for analysis. Toxicity criteria during initial 4 weeks study used to define maximum-tolerated dose (MTD). During this period, one patient withdrew deep vein thrombosis (DVT) probably caused by an undiagnosed primary melanoma lymphadenopathy groin, because progressive disease (PD), three discontinued neutropenia. Nineteen 24 continued on treatment beyond PD development event. Three further developed DVT at 4, 9, 11 months. Treatment resulted greater than 25% reduction paraprotein 67% patients, 13 (54%) experienced 50% paraprotein, four (17%) entered complete remission. The MTD 2 mg/d. showed increased CD45RO expression CD4(+) CD8(+) cells, concomitant decrease CD45RA(+) cells. associated significantly interleukin (IL)-2 receptor IL-12 levels, which is consistent activation T cells monocytes macrophages.This demonstrates safety efficacy orally This first report demonstrating vivo costimulation class compound, supporting potential role as immunostimulatory adjuvant treatment.