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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Given IV
Given IV
Scripps Clinic - La Jolla
La Jolla, California, United States
University of California San Diego
La Jolla, California, United States
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States
Northside Hospital
Atlanta, Georgia, United States
Dana-Farber Harvard Cancer Center
Boston, Massachusetts, United States
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
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
Kaplan- Meier estimates of probability will be used.
Time frame: Up to day 360 following antibody infusion
Overall survival
Kaplan- Meier estimates of probability will be used.
Time frame: Up to 360 days post-infusion
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