DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
RATIONALE: Combinations of biological substances in DT388IL3 fusion protein may be able to carry cancer killing substances directly to the cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of DT388IL3 fusion protein and to see how well it works in treating patients with acute myeloid leukemia or myelodysplastic syndromes.
Blastic Plasmacytoid Dendritic Cell Neoplasm
Plasmacytoid Dendritic Cell Leukemia
Biological: DT(388)IL3 fusion protein
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: flow cytometry
Other: immunoenzyme technique
Other: laboratory biomarker analysis
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Therapy Targeting the Interleukin-3 Receptor (IL3R) for Patients With Relapsed or Refractory and Elderly or Poor-Risk Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome With DTIL3 (IND# 11314): a Phase I/II Clinical Trial|
- Dose-limiting toxicity [ Designated as safety issue: Yes ]
- Toxicity profile [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Designated as safety issue: Yes ]
- Clinical response rate [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Anti-DT388IL3 antibodies at days 1, 15, and 30 [ Designated as safety issue: No ]
- Serum DT388IL3 levels and half-life [ Designated as safety issue: No ]
- Leukemia blast interleukin-3 receptor density at baseline [ Designated as safety issue: No ]
- Acute myeloid leukemia (AML) progenitor sensitivity to DT388IL3 [ Designated as safety issue: No ]
- Correlation of response to treatment with disease type (relapsed/refractory or poor-risk de novo AML or high-risk myelodysplastic syndromes) [ Designated as safety issue: No ]
|Study Start Date:||July 2006|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose of DT_388IL3 fusion protein in patients with refractory or relapsed or poor-risk acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS).
- Define the dose-limiting toxicities of this regimen in these patients.
- Measure the pharmacokinetics of this regimen in these patients.
- Measure the immune responses in patients treated with this regimen.
- Evaluate response and correlate with disease type (relapsed/refractory or poor-risk de novo AML or high-risk MDS), pretreatment marrow blast percentage, and leukemia blast interleukin-3 receptor density.
OUTLINE: This is a phase I, multicenter, dose-escalation study followed by a phase II, open-label study.
- Phase I: Patients receive DT_388IL3 IV over 15 minutes daily for 5 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of DT_388IL3 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: An additional 15 patients receive DT_388IL3 at the MTD as in phase I. Patients undergo serum and blast collection periodically for laboratory studies, including analysis of expression of interleukin-3 receptors and anti-DT_388IL3 antibodies at baseline. Samples are also analyzed by immunoenzyme assays and flow cytometry.
After completion of study treatment, patients are followed periodically for up to 5 years.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
|United States, Texas|
|Scott and White Cancer Institute||Recruiting|
|Temple, Texas, United States, 76502|
|Contact: Arthur E. Frankel, MD 254-724-0094|
|Study Chair:||Arthur E. Frankel, MD||Scott and White Hospital & Clinic|