MT2005-13R - Phase I Open Label, Single Arm, Dose Escalation Trial to Evaluate the Biodistribution and Safety of AHN-12 in Patients With Advanced Leukemia
- To establish that a dose of 150 mg/m² of nonradiolabeled anti-CD45 monoclonal antibody
AHN-12 results in normal biodistribution, normal-organ estimated radiation-absorbed
dose of less than 20 Gy, and estimated radiation-absorbed dose of no more than 13 Gy to
the red marrow.
- To determine the maximum tolerated dose of yttrium Y 90 anti-CD45 monoclonal antibody
- To determine the human anti-mouse antibody (HAMA) response.
- To define, preliminarily, the antitumor activity of ^90Y-AHN-12.
OUTLINE: This is a dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody
- Biodistribution: Patients receive nonradiolabeled monoclonal antibody AHN-12 IV and an
imaging dose of indium Y 111 monoclonal antibody AHN-12 (^111In-AHN-12) IV over 10
minutes on day 0. Patients undergo whole-body gamma-camera imaging immediately
following infusion, at 4-6 hours, and on days 1, 3, 4, and 7. Blood samples are
collected prior to each imaging for dosimetry calculations and pharmacokinetics.
Patients also undergo bone marrow biopsy 16-24 hours after infusion for dosimetry
calculations. Patients with the expected biodistribution of ^111In-AHN-12, an estimated
radiation-absorbed dose to the normal organ of < 20 Gy, an estimated radiation-absorbed dose
to the red marrow of ≤ 13 Gy, and a negative human anti-mouse antibody at day 7 proceed to
the therapy portion.
- Treatment: Patients receive nonradiolabeled anti-CD45 monoclonal antibody AHN-12 IV
over 60 minutes and escalating therapy doses of yttrium Y 90 anti-CD45 monoclonal
antibody AHN-12 (^90Y-AHN-12) IV over 10 minutes on day 7 or 8.
After completion of study treatment, patients are followed periodically for 1 year.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Biodistribution of nonradiolabeled anti-CD45 monoclonal antibody AHN-12
Within 1 hour, 4-6 hours, Days 1, 3, 4 and 7 post infusion
Linda J. Burns, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center at University of Minnesota||Minneapolis, Minnesota 55455|