NCT02998047

A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Actinium Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

Summary

1. Establish the MTD 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. Estimate progression-free survival (PFS) and overall survival

Detailed description

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 3 escalating dose levels in the trial (0.5 μCi/kg, 1 μCi/kg, and 1.5 μCi/kg). Each dose can be administered in up to 3-8 cycles providing that the total dose received per patient does not exceed 4.5 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, ≥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, 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. Minimum three to maximum six patients will be treated at each dose level, and dose escalation will proceed as follows: 1. Rules for dose escalation are: 1. If 0 of 3 patients have a DLT, escalate to the next dose level (Unless enrolling patients at the 0.25 µCi/kg dose level) 2. If 1 of 3 patients has a DLT, expand the cohort to 6 patients 3. If ≤1 of 6 patients has a DLT, escalate to the next dose level (Unless enrolling patients at the 0.25 µCi/kg dose level) 4. If ≥2 of 3 or ≥2 of 6 patients have a DLT, then the previous dose is the MTD (Unless enrolling patients at the 0.25 µCi/kg level, in which case the trial is terminated) 5. Three patients will start at the 0.50 uCi/kg dose. The next dose level will be 1.0 µCi/kg and the final dose level will be 1.5 µCi/kg. Dose de-escalation to 0.25 µCi/kg will occur if, at the 0.5 µCi/kg dose, there are ≥2 of 3 or ≥2 of 6 patients with a DLT. 2. If a patient has not progressed nor had CR by the end of a cycle, the patient can continue treatment for a maximum of three (1.5 µCi/kg), four (1.0 µCi/kg), or eight cycles (0.25 µCi/kg and 0.50 µCi/kg). All patients may receive GCSF support starting on Day 9 if clinically indicated and continuing until ANC\>1,000. After the dose escalation portion is completed, treat 3 additional patients at the highest established dose level to confirm MTD and establish that dose level as MTD.

Conditions

• Refractory Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Lintuzumab AC 225	Lintuzumab-Ac225 is an immunoconjugate \[antibody: anti-CD 33 antibody and radioactive isotope: Actinium (225Ac)\] for the treatment of multiple myeloma.

Timeline

• Start date: 2016-12-01
• Primary completion: 2020-05-01
• Completion: 2020-05-01
• First posted: 2016-12-20
• Last updated: 2022-03-08

Locations

5 sites across 1 country: United States