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

NCT ID: NCT00397579

Last Updated: 2019-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2017-07-27

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 Description

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.

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.

Conditions

Leukemia; Myelodysplastic Syndromes; Blastic Plasmacytoid Dendritic Cell Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SL-401

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.

Group Type: EXPERIMENTAL

DT388IL3

Intervention Type: DRUG

Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

Interventions

DT388IL3

Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Poor-risk AML, as defined by any of the following criteria:

• Treatment-related AML, unless associated with favorable cytogenetics (e.g., inversion 16, t[16;16], t[8;21], t[15;17]), and ineligible for stem cell transplantation
• Antecedent hematological disease (e.g., myelodysplastic syndromes, myelofibrosis, or polycythemia vera) that evolved to AML (≥ 20% blasts) and ineligible for stem cell transplantation
• De novo AML (must be > 70 years of age)
• AML with unfavorable cytogenetics (e.g., abnormalities of chromosomes -7, -5, 7q-, or 5q-; complex [≥ 3] abnormalities; or abnormalities of 11q23, excluding t[9;11], t[9;22], inversion 3, t[3;3], and t[6;9]), regardless of age, and ineligible for allogeneic stem cell transplantation
• High-risk myelodysplastic syndromes diagnosed by morphologic, histochemical, or cell surface marker criteria

• Resistant or intolerant to chemotherapy
• Ineligible for or unwilling to undergo immediate allogeneic stem cell transplantation
• Bone marrow index (i.e., percent cellularity × percent blasts) ≤ 40% at time of treatment
• No active CNS leukemia

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Bilirubin ≤ 1.5 mg/dL
• ALT and AST < 2.5 times upper limit of normal
• Albumin ≥ 3 mg/dL
• Creatinine ≤ 1.5 mg/dL
• LVEF ≥ 50%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 weeks after completion of study treatment
• No complicated medical or psychiatric problems that would preclude study compliance
• No concurrent serious uncontrolled infection or disseminated intravascular coagulation
• No myocardial infarction within the past 6 months
• No allergies to diphtheria toxin
• No requirement for oxygen

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No other concurrent antineoplastic drugs
• No concurrent radiotherapy
• No concurrent corticosteroids as antiemetics
• No concurrent hematopoietic growth factors (e.g., epoetin alfa, interleukin-11, filgrastim [G-CSF], or sargramostim [GM-CSF])
• No concurrent intravenous immunoglobins

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arthur E. Frankel, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

Frankel AE, Woo JH, Ahn C, Pemmaraju N, Medeiros BC, Carraway HE, Frankfurt O, Forman SJ, Yang XA, Konopleva M, Garnache-Ottou F, Angelot-Delettre F, Brooks C, Szarek M, Rowinsky E. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014 Jul 17;124(3):385-92. doi: 10.1182/blood-2014-04-566737. Epub 2014 May 23.

Reference Type: DERIVED

PMID: 24859366 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STU 012013-061

Identifier Type: -

Identifier Source: org_study_id