1. Establish the MTD of fractionated doses of Lintuzumab-Ac225 as monotherapy 2. Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR) 3. Confirm the safety profile of the treatment regimen 4. Determine changes in plasmocyte, T-cell and MDSC cell populations 5. Estimate progression-free survival (PFS) and overall survival.
The study is a multicenter, open label Phase I trial. Phase 1, dose-escalation : This study uses a 3+3 design to estimate the maximum tolerated dose (MTD).
There will be 2 escalating dose levels in the trial (0.5 μCi/kg and 1 μCi/kg,). Each dose can be administered in up to 4-8 cycles providing that the total dose received per patient does not exceed 4 μCi/kg.
De-escalation (decrease dose level to 0.25 μCi/kg) is planned if at the first dose level of 0.5 μCi/kg, after expanding the cohort to a maximum of 6 patients, ≥1/3 patients have M protein decrease >10% AND ≥2 patient have DLTs. At the dose level of 0.25 μCi/kg, if eligible to continue receiving additional doses of the study drug, patients will receive up to 8 doses in total, with the total administered activity being 2 μCi/kg.
The starting dose level will be 0.5 μCi/kg of 225Ac-Lintuzumab administered on day 1 of each cycle. If this dose level is safe, the second dose level of 1 μCi/kg will be explored. If the starting dose level results in DLTs in ≥2 patients and ≥1/3 patients have M protein decrease >10%, the dose level of 0.25 μCi/kg will be explored.
Subjects will receive the investigational drug as a single infusion at the prescribed dose level.
Intra cohort dose escalation/ decrease is not allowed.
The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.
The following criteria is provided for health care professionals.
Target Disease Exceptions
Medical History and Concurrent Diseases