Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies
The purpose of this study is to find a safe dose of actinium-225 when it is labeled to HuM195. This will be done with a "phase I trial," in which a preset schedule of doses gets more powerful for each new group of patients as the trial progresses. If too many serious side effects are seen with a certain dose, no one will be treated with a higher dose, and some additional patients may be treated with a lower dose to make sure that this dose is safe. The starting dose of actinium-225 in this study is less than doses that are known to be safe in animals.
Antibodies are proteins that are produced by the immune system and help the body to fight foreign substances, such as bacteria or viruses. HuM195 was made by putting human leukemia cells into mice. Most of the mouse parts of this antibody were replaced with human parts. Only the part of the antibody that binds to the leukemia cells was kept from the mouse. HuM195 attaches to leukemia cells but does not attach to most normal cells. It can kill small amounts of disease by identifying the leukemia cells as "foreign." HuM195 has worked less well against large amounts of leukemia since the normal immune cells needed to kill leukemia cells are lowered in most patients with leukemia.
|Leukemia Myelodysplastic Syndrome||Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of Targeted Atomic Nano-Generators (Actinium-225-Labeled Humanized Anti-CD33 Monoclonal Antibody HuM195) in Patients With Advanced Myeloid Malignancies|
- To determine the maximum tolerated dose of 225Ac-HuM195 that can be administered to patients with advanced myeloid leukemias. [ Time Frame: conclusion of study ]
- To determine the pharmacokinetics and dosimetry of 225Ac-HuM195. [ Time Frame: conclusion of the study ]
- To determine the biological effects of 225Ac-HuM195, including its ability to produce complete remissions. [ Time Frame: conclusion of the study ]
|Study Start Date:||July 2005|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
This is a phase I, dose-escalation trial. The starting dose level will be 0.5 μCi/kg of 225Ac-HuM195. 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. Six patients will be treated at the maximum tolerated dose
Biological: ACTINIUM-225-LABELED HUMANIZED ANTI-CD33 MONOCLONAL ANTIBODY HuM195
A single infusion of 225Ac-HuM195 will be administered at a starting dose of 0.5 μCi/kg. Additionally, 100 mCi of 213Bi-HuM195 have been administered with full dose cytarabine (200 mg/m2 daily for 5 days) without dose-limiting toxicity.Serial sampling of blood, urine, and bone marrow will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antileukemic effects. Three to six patients will be treated at each dose level. Dose escalation will proceed if less than 33% of patients in a cohort experience dose-limiting toxicity.Patients will be followed until completion of therapy as outlined in the study, loss to follow-up, death, or until the day the patient is removed from the study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00672165
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Dan Douer, MD||Memorial Sloan Kettering Cancer Center|