Phase I Study of Thrice Weekly Hu1D10*in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Acute Leukemia
I. Determine the maximum tolerated dose (MTD) or biological effective dose of monoclonal
antibody Hu1D10 (apolizumab) in patients with previously treated chronic lymphocytic
leukemia or small lymphocytic lymphoma.
II. Determine the safety of this drug, in terms of frequency and severity of
treatment-related adverse events, in this patient population.
I. Determine whether this drug has anti-leukemia/lymphoma activity in patients expressing
the Hu1D10 antigen.
II. Determine the pharmacokinetics of this drug in this patient population. III. Determine
whether the infusion-related toxicity of this drug is secondary to cytokine release in these
IV. Determine whether the intensity of 1D10 target antigen on tumor cells is related to
clinical response and treatment toxicity in these patients.
V. Determine the pharmacodynamics of this drug in this patient population.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
diagnosis (chronic lymphocytic leukemia or small lymphocytic lymphoma vs acute lymphoblastic
leukemia [ALL] or acute myeloid leukemia [AML]). Patients with ALL or AML are enrolled after
the maximum tolerated dose (MTD) is determined.
Patients receive apolizumab IV over at least 2 hours on days 1, 2, 3, 5, 8, 10, 12, 15, 17,
19, 22, 24, and 26. Treatment continues in the absence of disease progression or
unacceptable toxicity. Patients with a complete or partial response who relapse after 2
months may receive an additional course of therapy provided they still express the 1D10
Cohorts of 3-6 patients receive escalating doses of MOAB Hu1D10 until the MTD is determined.
The MTD is defined as the dose preceding that at which 2 of 6 patients experience
dose-limiting toxicity (DLT). If no DLT is observed, the biological effective dose (BED) is
determined in the above cohorts. The BED is defined as the dose at which at least 4 of 6
patients experience an acceptable minimum trough level and clinical response. An additional
24 patients (12 per stratum) are treated at the MTD.
Patients are followed at 1 week, 1 and 2 months, and then every 3 months for 1 year.
PROJECTED ACCRUAL: A total of 35 patients (12 per stratum) will be accrued for this study.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as the dose level below which two or more of six patients experience a DLT assessed using NCI CTC version 2.0
Up to 30 days
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|