Phase II Maraviroc for GVHD Prevention
RATIONALE: Successful allogeneic stem-cell transplantation is often limited by graft-versus-host disease (GVHD). Migration of donor cells into tissues plays a major role in GVHD. Drugs that block chemokine receptors such as CCR5, can potentially decrease the migration of donor cells into tissues. Blocking CCR5 after allogeneic stem-cell transplantation may therefore reduce the rates of GVHD.
PURPOSE: This study explores the efficacy of pharmacologic inhibition of CCR5 in prevention of GVHDby administering maraviroc during allogeneic stem-cell transplantation with reduced intensity conditioning.
Hematologic Malignancy Requiring Allogeneic Stem-cell Transplantation.
Drug: Maraviroc 300 mg
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase II Study to Assess the Efficacy of Maraviroc, a CCR5-Antagonist in Prophylaxis of Graft-Versus-Host Disease in Patients With Hematologic Malignancies Undergoing Reduced-Intensity Allogeneic Stem-Cell Transplantation From Unrelated Donors|
- Number of Serious Adverse Events [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]The cumulative incidence of grade 2-4 acute GVHD by day 180 after the stem-cell infusion
|Study Start Date:||February 2013|
|Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
To estimate the cumulative incidence of grade 2-4 acute GVHD by day 180 with the addition of maraviroc to a standard prophylaxis regimen in patients with hematologic malignancies undergoing reduced intensity allogeneic stem-cell transplantation (RIC SCT) from unrelated donors.
- To assess the toxicity of a prolonged administration of maraviroc in patients undergoing RIC SCT.
- To estimate the rates of severe (grade 3-4) acute GVHD by day 100 and 180, grade 2-4 acute GVHD by day 100, organ-specific acute GVHD, chronic GVHD, relapse, infections, non-relapse mortality, use of immunosuppressive therapies and 1-year survival in patients treated with maraviroc after RIC SCT.
- To assess the effect of treatment with maraviroc on immune recovery, engraftment and donor T-cell chimerism in peripheral blood and in target organs.
- To assess the effect of donor and recipient CCR5 genotype on the incidence of acute GVHD in patients receiving maraviroc as part of a GVHD prophylaxis regimen.
OUTLINE: Patients receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis. In addition, all patients receive maraviroc from day -3 to d+ 90.
Patients are followed for 1 year after the stem-cell infusion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01785810
|United States, Pennsylvania|
|Abramson Cancer Center of the University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||David Porter, MD||Abramson Cancer Center of the University of Pennsylvania|