Clinical Trial: Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: CTLA-4 Blockade With MDX-010 to Induce Graft-Versus-Malignancy Effects Following Allogeneic Hematopoietic Stem Cell Transplantation

Brief Summary: This phase I trial is studying how well ipilimumab works after allogeneic stem cell transplant in treating patients with persistent or progressive cancer. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the dose of MDX-010 (ipilimumab) that can safely be administered to patients with persistent or progressive malignancy following allo-HCT.

II. To determine the pharmacokinetics of different doses of MDX-010 administered as a single dose to patients with persistent or progressive malignancy following allo-HCT.

III. By assessment of aims 1 and 2, to determine the best dosing regimen for further study of CTLA-4 blockade in conjunction with escalating dose donor-leukocyte infusions (DLI) in patients with evidence of residual or progressive malignancy following allo-HCT.

IV. To assess if there is preliminary evidence of efficacy following the administration of MDX-010 in this population.

OUTLINE:

Patients receive ipilimumab intravenously (IV) over 90 minutes.

Cohorts of 3-6 patients receive escalating doses of ipilimumab until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients with persistent or progressive disease at 60 days after ipilimumab administration and no evidence of graft-versus-host disease receive donor lymphocyte infusions every 60 days for a total of 3 infusions.

Patients are followed at 4, 5, 6, 9, and 12 months and then annually thereafter.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Incidence of grade 3 and 4 acute GVHD based on NCI CTC [ Time Frame: 60 days following administration of ipilimumab ]
  • Incidence of graft rejection following ipilimumab defined as the percentage of patients entered who demonstrate =< 10% donor T-cell chimerism [ Time Frame: Post-infusion day 60 ]
  • Autoimmune reaction defined as >= grade 3 dysfunction of a vital organ or the graft [ Time Frame: Up to 5 years ]


Original Primary Outcome:

Current Secondary Outcome:

  • Polyclonal T-cell activation monitored by clinical assessment and laboratory evidence (anti CD3, CD4, CD8) and markers of activation (anti CD69, CD25, CD44 and MHC class II) [ Time Frame: Up to 5 years ]
  • Incidence of extensive stage chronic GVHD [ Time Frame: Post-infusion day 360 ]
  • Disease response [ Time Frame: Up to day 360 post ipilimumab infusion ]
  • Disease-free survival [ Time Frame: Up to day 360 following antibody infusion ]
    Kaplan- Meier estimates of probability will be used.
  • Overall survival [ Time Frame: Up to 360 days post-infusion ]
    Kaplan- Meier estimates of probability will be used.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 6, 2003
Date Started: April 2003
Date Completion:
Last Updated: March 26, 2013
Last Verified: March 2013