A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma
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|ClinicalTrials.gov Identifier: NCT02998047|
Recruitment Status : Recruiting
First Posted : December 20, 2016
Last Update Posted : December 18, 2018
- Establish the MTD of Lintuzumab-Ac225 as monotherapy
- Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR)
- Confirm the safety profile of the treatment regimen
- Estimate progression-free survival (PFS) and overall survival
|Condition or disease||Intervention/treatment||Phase|
|Refractory Multiple Myeloma||Drug: Lintuzumab AC 225||Phase 1|
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:
Rules for dose escalation are:
- 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)
- If 1 of 3 patients has a DLT, expand the cohort to 6 patients
- 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)
- 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)
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||January 2020|
Experimental: IV infusion of Lintuzumab AC225
Starting dose - 0.5 μCi/Kg IV infusion of Lintuzumab AC225 on Day 1 of each cycle with dose escalation 1 μCi/Kg and 1.5 μCi/Kg or de-escalation to 0.25 μCi/Kg.
1 cycle = 28 days, up to 3 to 8 cycles (depending on the cohort).
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.
Other Name: HuM195-Ac225
- Maximum Tolerated dose of Lintuzumab-AC225 [ Time Frame: Through study completion, an average of 2.5 year ]
- Adverse events- Treatment Emergent [ Time Frame: Through study completion, an average of 2.5 year ]
- Response rates (objective response rate, complete response rate, stringent complete response rate, very good partial response rate and partial response rate) [ Time Frame: Through study completion, an average of 2.5 year ]
- Progression free survival [ Time Frame: Through study completion, an average of 2.5 year ]
- Overall survival [ Time Frame: Through study completion, an average of 2.5 year ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02998047
|Contact: Actinium Pharmaceuticals,Inc (Director of Clinical Operations)||firstname.lastname@example.org|
|United States, California|
|Los Angeles, California, United States, 90095|
|United States, Kansas|
|University Of Kansas Medical Center||Recruiting|
|Kansas City, Kansas, United States, 66205|
|United States, Texas|
|Baylor Scott and White Research Institute, Charles A. Sammons Cancer Center||Recruiting|
|Dallas, Texas, United States, 75246|
|Study Director:||Mark Berger, MD||Actinium Pharmaceuticals|