Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)
Acute Myelogenous Leukemia
Chronic Myelomonocytic Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia (AML) and Chronic Myelomonocytic Leukemia (CMML)|
|Study Start Date:||December 2003|
|Study Completion Date:||December 2004|
|Primary Completion Date:||December 2004 (Final data collection date for primary outcome measure)|
Starting dose of DTGM fusion protein 2 mcg/kg/day as a short (30 min) intravenous infusion, three times /week (M,W,F) for two consecutive weeks. In absence of defined grade 3/4 nonhematological toxicities in the first 0/3 or 1/6 patients, the dose will be escalated by 1 mcg/kg/day for the next patient cohort.
Starting dose: 2 mcg/kg by vein three times a week (M,W,F) for two consecutive weeks.
Other Name: Diphtheria toxin fused with granulocyte macrophage colony stimulating factor
The majority of malignant myeloid progenitor cells express receptors for GM-CSF. The fusion of GM-CSF with diphtheria toxin allows a targeting of cells with GM-CSF receptors for effects of the toxin while sparing GM-CSF receptor-lacking multipotent stem cells. The great majority of AML cells express GM-CSF receptors and DT388GMCSF has shown selective killing of AML and CMML progenitors in vitro while sparing normal progenitor cells. When administered as a single bolus to rodents, adequate blood DT388GMCSF biological activity was found to kill several logs of leukemic cells. A phase I clinical trial of DT388GMCSF given as a daily bolus i.v. infusion for up to 5 consecutive days was completed in 38 patients. The study defined liver toxicity as the DLT. The liver toxicity was observed only in patients > 50 years and receiving steroids. Responses were seen in four patients consisting of one complete remission and 3 partial remission of short duration. Peak drug levels were inversely proportional to pre-treatment DT388GMCSF antibody levels.
Because of the observed significant preclinical activity in AML and CMML, clinical activity in chemorefractory patients with AML, the association of toxicities with steroid exposure, and association of the drug level with antibody titer that could be decreased with DT388GMCSF exposure, the current follow up phase I trial is designed based on a new administration and is a dose - finding trial also aimed to better determine and control side effects, improve drug pharmacokinetics and provide initial insight into antileukemic activity of this novel agent, delivered at a prolonged intermittent schedule.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00074750
|United States, Texas|
|The University of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Miloslav Beran, MD, PhD, DVM||M.D. Anderson Cancer Center|