Phase I Evaluation of the Anti-CD-33 Immunotoxin Hum-195/rGel in Patients With Advanced Myeloid Malignancies
Before therapy, all patients will be asked about their medical history, and a physical exam
(with measurement of vital signs) will be performed. A chest X-ray and an electrocardiogram
(ECG - a test to measure the electrical activity of the heart) will be performed. Blood
(about 4 teaspoons) will be drawn for routine tests and blood clotting tests. Women who are
able to become pregnant will have a urine pregnancy test done. A test will be done to
measure the amount of oxygen in your blood by placing a monitoring device on your finger.
Blood (about 1 teaspoon) will be taken to measure the amount of a protein that is present on
the diseased cells. During the study period, the study staff will draw blood samples for
routine tests, pharmacokinetic (PK) tests, and anti-drug antibody tests. Blood (about 1
teaspoon) will be drawn to measure the amount of a protein that is present on the diseased
cells. A bone marrow sample will also be obtained before treatment and on Study Day 28.
Patients will receive four injections of the immunotoxin. The immunotoxin is designed to
selectively destroy myeloid leukemia cells. The injections will be given through a vein
twice weekly for two weeks. Patients will then be evaluated twice weekly for the next two
weeks. If there has been improvement in the leukemia, or if the leukemia has remained
stable and there have been no serious side effects of treatment, patients will then receive
a second course of immunotoxin injections. These will again be given twice weekly for two
weeks. Depending on the effectiveness against leukemia and the side effects, patients may
receive maintenance treatment. This would also consist of two weekly injections given for
two weeks followed by two weeks of observation. Maintenance therapy may continue for up to
four months for partial response and up to two months for complete response.
This is an investigational study. Up to 36 patients will take part in this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose (MTD)
Dose-limiting toxicity considered to have occurred when (1) >grade 2 extramedullary toxicity possibly related to HuM195/rGel (except nausea, vomiting or diarrhea unless uncontrolled by optimal management, or electrolyte abnormalities unless clinically significant or not correctable after optimal replacement) is observed or (2) >42 days from day 1 of therapy elapse before return of neutrophil count to >500 and platelet count to >25,000 in absence of leukemia (i.e., with a normal or hypercellular bone marrow with <5% blasts).
Continuous assessment of safety throughout entire study period and determination of dose-limiting toxicities at end of two week evaluation period (4 weeks from start of therapy).
Jorge Cortes, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
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