A Phase I Study of DTGM Fusion Protein (IND BB#8153) in Relapsed and Refractory Adult Acute Myeloid Leukemia (AML)

OBJECTIVES: I. Determine the maximum tolerated dose of DTGM fusion protein in patients with recurrent or refractory adult acute myeloid leukemia. II. Determine the dose-limiting toxic effects of this regimen in these patients. III. Measure the pharmacokinetics of this regimen in these patients. IV. Evaluate the response rate at the maximum tolerated dose and immune responses in patients treated with this regimen. V. Correlate in vitro sensitivity of leukemic blasts to this regimen with the response rate in these patients. VI. Correlate tumor necrosis factor genetic polymorphisms with toxicity profiles and dose-limiting toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study. Patients are stratified according to serum level of anti-DTGM antibody titer (2 mg/L or less vs greater than 2 mg/L). Patients receive DTGM fusion protein IV over 15 minutes on days 1-5. Patients with a partial response are eligible for retreatment. Cohorts of 3-6 patients receive escalating doses of DTGM fusion protein until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with DTGM fusion protein at the MTD. Patients are followed monthly until disease progression.

PROJECTED ACCRUAL: Approximately 60 patients will be accrued for this study within 3 years.