Clinical Trial: DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

Brief Summary:

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.

Detailed Summary:

OBJECTIVES:

• 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.

Treatment:

Patients will be treated with a maximum of five doses of approximately 15min IV infusions of DT388IL3/SL-401 over a ten day period at a maximum of once daily.

Response to Treatment will be evaluated as follows:

1. Complete response (CR): patient has a normal whole blood count; platelets with absent blasts in peripheral blood or marrow; no evidence of nodal involvement or liver/spleen involvement; no skin lesion involvement.
2. Partial Response (PR); patient experiences a decrease of 50% or more in marrow blasts and skin lesions; and there is a decrease in the size of the nodes/liver/spleen.
3. Stable Disease (SD); failure to achieve at least PR, and there is no evidence of progression for 2 months.
4. Failure: death during treatment or disease progression characterized by an increase in the percentage bone marrow blast or an increase in skin or node/liver or spleen size.