Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients
The goal of the Phase 1 part of this study is to find the highest tolerable dose of Lintuzumab-Ac225 that can be given with cytarabine to patients with acute myeloid leukemia (AML).
The goal of the Phase 2 part of this study is to learn if Lintuzumab-Ac225 and cytarabine can control AML. The safety of this drug combination will also be studied.
Lintuzumab-Ac225 is designed to deliver radiation therapy directly inside leukemia cells without giving any radiation to the surrounding normal cells
Cytarabine is designed to insert itself into DNA (genetic material) of cancer cells and stop the DNA from repairing itself.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- Maximum Tolerated Dose (MTD) of Lintuzumab-Ac225 [ Time Frame: Cycle 1, up to 52 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2012|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Cytarabine + Lintuzumab-Ac225
Cytarabine 20 mg subcutaneously every 12 hours Days 1 to 10 of every cycle. Starting dose level 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. Lasix 40 mg by mouth (po) daily one day prior to treatment with Lintuzumab-Ac225 and continuing for 10 days following administration of the 2nd divided dose. Spironolactone, 25 mg po daily, administered 11 days after second dose of 225Ac-HuM195 (the day after completion of furosemide) and continued for 12 months.
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
Starting dose level 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.
Other Name: LintuzumabDrug: Lasix
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: furosemideDrug: Spironolactone
25 mg by mouth daily, administered 11 days after second dose of 225Ac-HuM195 (the day after completion of furosemide) and continued for 12 months.
If found to be eligible to take part in this study, participants will be assigned to a study group based on when joining the study. Up to 4 groups of up to 6 participants will be enrolled in the Phase I portion of the study, and up to 53 participants will be enrolled in Phase II.
If enrolled in the Phase I portion, the dose of Lintuzumab-Ac225 received will depend on when participant joined this study. The first group of participants will receive the lowest dose level of Lintuzumab-Ac225. Each new group will receive a higher dose of Lintuzumab-Ac225 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of Lintuzumab-Ac225 is found.
If enrolled in the Phase II portion, participant will receive Lintuzumab-Ac225 at the highest dose that was tolerated in the Phase I portion.
All participants will receive the same dose level of cytarabine.
Study Drug Administration:
Participants will receive cytarabine as an injection under the skin. This is called a subcutaneous injection. During the first office visit, participant or a caregiver will be taught to give these injections at home. Participant will get cytarabine injections 2 times each day during Days 1-10 of each study cycle. Cycle 1 may last up to 52 days and will depend on how participant recovers from the Lintuzumab-Ac225. All other cycles will be 28 days.
Participant will receive Lintuzumab-Ac225 by vein over 15-30 minutes at a time point about 4 to 7 days after your last dose of cytarabine in Cycle 1. Participant will receive it a second time about 4 to 7 days after that.
One (1) day before the second dose of Lintuzumab-Ac225, participant will begin taking lasix (furosemide) by mouth every day for 10 days. Furosemide is taken to prevent possible damage to the kidneys.
One (1) day after last dose of furosemide, participant will begin taking spironolactone by mouth every day for up to 1 year. It is also taken to prevent possible kidney damage.
|Contact: Farhad Ravandi-Kashani, MD||713-745-0394|
|United States, Texas|
|UT MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Principal Investigator: Farhad Ravandi-Kashani, MD|
|Study Chair:||Farhad Ravandi-Kashani, MD||UT MD Anderson Cancer Center|