Low Dose Cytarabine and Lintuzumab-Ac225 in Older AML Patients
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) to fractionated doses of Lintuzumab-Ac225 alone (Phase 2 portion)
|AML||Drug: Cytarabine (Phase 1 only) Biological: Lintuzumab-Ac225 Drug: Furosemide (Phase 1 only) Drug: Spironolactone||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients With Untreated Acute Myeloid Leukemia|
- 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 [ Time Frame: Up to 22 weeks from enrollment ]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 ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||February 2019|
|Estimated Primary Completion Date:||May 2018 (Final data collection date for primary outcome measure)|
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.
Other Names:Biological: Lintuzumab-Ac225
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.
Other Names: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: LasixDrug: Spironolactone
25 mg by mouth daily, administered 10 days after second dose of 225Ac-HuM195 and continued for 12 months.
Other Name: Aldactone
Please refer to this study by its ClinicalTrials.gov identifier: NCT02575963
|Contact: Actinium Pharmaceuticals,Inc (Director of Clinical Operations)||firstname.lastname@example.org|
|United States, Kentucky|
|University of Kentucky, Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40536|
|United States, Louisiana|
|Ochsner Medical Center, The Gayle and Tom Benson Cancer Center||Recruiting|
|New Orleans, Louisiana, United States, 70121|
|United States, New York|
|Columbia University Medical, Herbert Irving Comprehensive Cancer Center||Recruiting|
|New York, New York, United States, 10032|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|United States, Pennsylvania|
|University of Pennsylvania, Perelman Center for Advanced Medicine||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, South Carolina|
|St. Francis Cancer Center||Recruiting|
|Greenville, South Carolina, United States, 29607|
|United States, Texas|
|Baylor Scott and White Research Institute, Charles A. Sammons Cancer Center||Recruiting|
|Dallas, Texas, United States, 75246|
|United States, Washington|
|Swedish Cancer Institute, Center for Blood Disorders and Stem Cell Transplantation||Recruiting|
|Seattle, Washington, United States, 98104|
|Fred Hutchinson Cancer Research Center||Recruiting|
|Seattle, Washington, United States, 98109|
|United States, West Virginia|
|West Virginia University, Mary Babb Randolph Cancer Center||Recruiting|
|Morgantown, West Virginia, United States, 26506|
|United States, Wisconsin|
|Medical College of Wisconsin Cancer Center||Recruiting|
|Milwaukee, Wisconsin, United States, 53226|
|VA Caribbean Healthcare System||Recruiting|
|San Juan, Puerto Rico, 00921|
|Study Director:||Mark Berger, MD||Actinium Pharmaceuticals Inc.|