Lintuzumab-Ac225 in Older Acute Myeloid Leukemia (AML) Patients
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|ClinicalTrials.gov Identifier: NCT02575963|
Recruitment Status : Completed
First Posted : October 15, 2015
Last Update Posted : March 9, 2022
The study is a multicenter, open label Phase I/II trial.
- Establish the MTD of fractionated doses of Lintuzumab-Ac225 in combination with low dose cytosine arabinoside (Low Dose Ara-C, LDAC) (Phase 1 portion)
- Determine the response rate (CR + CRp + CRi) to fractionated doses of Lintuzumab-Ac225 alone (Phase 2 portion)
|Condition or disease||Intervention/treatment||Phase|
|AML||Drug: Cytarabine (Phase 1 only) Biological: Lintuzumab-Ac225 Drug: Furosemide (Phase 1 only) Drug: Spironolactone||Phase 1 Phase 2|
The study is a multicenter, open label Phase I/II trial. Phase I, dose-escalation: This portion of the overall study uses a 3+3 design to estimate the maximum tolerated dose (MTD). The starting dose level will be 1.0 μCi/Kg of Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractionated doses (0.5 μCi/Kg and 7.5 μg /Kg + 0.5 μCi/Kg and 7.5 μg /Kg) with the first fraction administered approximately 4 - 7 days after 1 cycle of LDAC (20 mg subQ every 12 h x 10 days administered for cytoreduction) and the second fraction administered 4-7 days after the first fraction. Subjects will then go on to receive up to 11 additional cycles of LDAC or until progression of disease. Three to six patients will be treated at each dose level, and dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.
Phase II, efficacy component. The study was designed as a 2- stage minimax design. Patients will be given two infusions of Lintuzumab-Ac225, 4-8 days apart (Day 5-Day 9), initially at the dose level determined to be the MTD in the Phase I portion. The second dose of Lintuzumab-Ac225 may be delayed up to 14 days after the first dose for clinical or scheduling reasons. Response will be initially assessed on or around days 28-42 after the final study drug administration. The primary endpoint (CR+CRp + CRi) will be determined on day 42. Best response will be evaluated from Day 1, Dose 1 until the end of the study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia|
|Study Start Date :||October 2012|
|Actual Primary Completion Date :||November 2018|
|Actual Study Completion Date :||May 2020|
Experimental: Phase 1 (Completed)
Cytarabine + Lintuzumab-Ac225 Cytarabine days 1 to 10 of each cycle. Doses were divided into 2 equal fractions with the first fraction given approx. 4-7 days after 1 cycle of low dose cytarabine and the second fraction given 4-7 days after the first fraction, followed by up to 11 more cycles. Furosemide (Phase 1 only) and Spironolactone were administered after Lintuzumab-Ac225.
Experimental: Phase 2
Experimental: Lintuzumab-Ac225 The Phase II dose determined during the Phase I dose escalation was 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8. Spironolactone is administered after Lintuzumab-Ac225.
Drug: Cytarabine (Phase 1 only)
Low dose cytarabine administered at 20 mg subcutaneously every 12 hours for the first 10 days (Days 1 to 10) of every cycle. Cycle 1 can last up to 52 days (depending on the schedule of study drug dosing) in order to allow for recovery from Lintuzumab-Ac225. Cycles 2-12 will last 28 days each.
In Phase 1 the starting dose level was 1.0 μCi/Kg of Lintuzumab-Ac225 and 15 μg/Kg unlabeled HuM195 divided into 2 equal fractionated doses (0.5 μCi/Kg and 7.5 μg /Kg + 0.5 μCi/Kg and 7.5 μg /Kg) with the first fraction administered approximately 4-7 days after 1 cycle of low dose cytarabine and the second fraction administered 4-7 days after the first fraction, followed by up to 11 more cycles. In Phase 2 the dose will be 4.0 μCi/Kg Lintuzumab-Ac225 and 25 μg/Kg unlabeled HuM195 divided into 2 equal fractions with the first fraction given on Day 1 and the second fraction given on Day 5-8.
Drug: Furosemide (Phase 1 only)
40 mg by mouth daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose.
Other Name: Lasix
25 mg by mouth daily, administered 10 days after second dose of 225Ac-HuM195 and continued for 12 months.
Other Name: Aldactone
- Phase I: Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 [ Time Frame: Cycle 1, up to 52 days ]If two or more patients in a cohort experience dose limiting toxicity (DLT), then maximum tolerated dose (MTD) will have been exceeded, and no further dose escalation will occur. If only three patients were treated at a dose level under consideration as the MTD, then up to three additional patients will be accrued. If no more than one of the six patients at that dose level experiences DLT, then that dose level will be confirmed as the MTD.
- Phase II: CR+CRp+CRi [ Time Frame: First evaluation at 42 days after treatment ]The primary objective is to determine the antileukemic effects, including its ability to produce complete remissions, of Lintuzumab-Ac225.
- Phase II: PFS [ Time Frame: 1 year ]Progression Free Survival
- Phase II: LFS [ Time Frame: 1 year ]Leukemia Free Survival
- Phase II: OS [ Time Frame: 1 year ]Overall Survival
- Phase II: Toxicity Spectrum [ Time Frame: 1 year ]Safety Data
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): NCT02575963
|Study Chair:||Avinash Desai, MD||Actinium Pharmaceuticals Inc.|