Phase I/II Study of Anti-CTLA-4 Monoclonal Antibody (MDX-010) in B-cell Non-Hodgkin's Lymphoma
I. To characterize the safety profile of MDX-010 (ipilimumab) monoclonal antibody and
identify a tolerable immunologically active dose level in B cell lymphoma patients.
II. To evaluate the clinical response rate in B cell lymphoma patients treated with MDX-010.
I. To evaluate the phenotype and function of memory T cells before and after treatment with
- Quantitation and phenotypic characterization of peripheral blood and tumor infiltrating
T-cells, including cluster of differentiation (CD)4+CD25+ regulatory T cells.
- Measurement of tumor-specific T cells in peripheral blood lymphocytes.
- Measuring proliferation of memory T cells in response to recall antigens (tetanus
toxoid and keyhole limpet hemocyanin [KLH]).
II. Measurement of anti-tumor antibodies in serum pre- and post-therapy. III. To evaluate
the time to progression. IV. To evaluate the duration of response to treatment with MDX-010.
OUTLINE: This is a multicenter, open-label, phase I, dose-escalation study followed by a
phase II study. Patients are grouped according to prior treatment with a vaccine therapy for
lymphoma (yes vs no).
PHASE I: Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal
antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total
of 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients from each group receive escalating doses of MDX-010 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive MDX-010 as in phase I at the MTD.
Patients are followed at 1 and 4 months and then every 6 months for up to 2 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Overall Confirmed Responses(Complete Response or Partial Response)
Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.
From registration to month 7
United States: Food and Drug Administration
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