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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02998047
|Contact: Actinium Pharmaceuticals,Inc (Director of Clinical Operations)||email@example.com|
|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|