A Phase I Study of Lintuzumab-Ac225 in Patients With Refractory Multiple Myeloma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02998047|
Recruitment Status : Recruiting
First Posted : December 20, 2016
Last Update Posted : October 20, 2017
- Establish the MTD of fractionated doses of Lintuzumab-Ac225 as monotherapy
- Establish overall response rate (ORR) where ORR = CR + sCR+ VGPR+PR)
- Confirm the safety profile of the treatment regimen
- Determine changes in plasmocyte, T-cell and MDSC cell populations
- 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 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.
Minimum three to maximum six patients will be treated at each dose level, and dose escalation will proceed as follows:
- if 1/3 patients have M protein decrease >10% on Day 42 AND no patients have DLTs, redose at the same dose level by Day 60 if ANC and PLT counts allow;
- if 1 patient at the given dose level has DLTs, expand the cohort by adding 3 more patients at that dose level.
- if 1/3 of patients in the expanded cohort exhibit DLTs, proceed to the next dose level.
- if at the first dose level,after expanding the cohort to a maximum of 6 patients .1/3 patients have M protein decrease >10% AND .2 patient has DLTs, decrease dose level to 0.25 uCi/kg
- if no patients at the reduced dose level of 0.25 uCi/kg have M protein decrease >10% AND 1 patient has DLTs terminate trial
- if none of the patients have DLTs at the given dose level, escalate to the next dose level.
- if 2 or more patient exhibit DLTs at any given dose level, the previous dose level will be considered MTD.
- if 2/3 patients respond with PR or better and <1/3 patients have DLTs, complete Phase 1 portion at that dose level (no further dose escalation).
- if patients who have at least stable disease are eligible to receive an additional cycle of treatment by Day 60 and their response status remains worse than CR, they will continue receiving repeated doses of study drug every 60 days after cycle 2 until they have received a cumulative dose of up to 4 ìCi/kg or until they achieve CR, whichever is sooner.
All patients will receive GCSF support starting on Day 9 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 or de-escalation to 0.25 μCi/Kg. 1 cycle = 42 days, up to 8 cycles. Re-dosing is done no sooner than 60 days.
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)||firstname.lastname@example.org|
|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|