Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00074750
Status:
TERMINATED
Last Update Posted:
2012-02-22
First Post:
2003-12-19
Brief Title:
Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia AML and Chronic Myelomonocytic Leukemia CMML
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
A Phase I Study of DT388GMCSF Fusion Protein in Acute Myelogenous Leukemia AML and Chronic Myelomonocytic Leukemia CMML
Status:
TERMINATED
Status Verified Date:
2012-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
DTGM belongs to a new generation of drugs designed to target leukemic cells To achieve this DTGM takes advantage of the ability of naturally-produced growth factor GM granulocyte-macrophage stimulating factor to deliver a drug diphtheria toxin to cells preferably leukemic cells It then attaches to the cells and allows the toxin to enter the leukemic cells and destroy them
Detailed Description:
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 iv 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
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None