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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Texas Southwestern Medical Center
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00397579
First received: November 8, 2006
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Blastic Plasmacytoid Dendritic Cell Neoplasm
Drug: DT388IL3
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
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

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Response Measurements [ Time Frame: treated over a 10 day period ] [ Designated as safety issue: Yes ]

    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.


Estimated Enrollment: 9
Study Start Date: July 2006
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: DT388IL3
Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Histologically or morphologically confirmed acute myeloid leukemia (AML), meeting 1 of the following criteria:

      • Relapsed or refractory AML after treatment with ≥ 1 prior conventional induction therapy

        • Patients in early first relapse must not have a matched donor available and/or be ineligible for allogeneic stem cell transplantation
      • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00397579

Contacts
Contact: Joyce Bolluyt 214-648-7007 joyce.bolluyt@UTSouthwestern.edu

Locations
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Arthur E. Frankel, MD    214-648-4180      
Principal Investigator: Arthur Frankel, MD         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Arthur E. Frankel, MD UT Southwestern Medical Center
  More Information

No publications provided

Responsible Party: University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT00397579     History of Changes
Other Study ID Numbers: 012013-061
Study First Received: November 8, 2006
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Texas Southwestern Medical Center:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
secondary acute myeloid leukemia
untreated adult acute myeloid leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
blastic plasmacytoid dendritic cell neoplasm
plasmacytoid dendritic cell leukemia
CD123+

Additional relevant MeSH terms:
Neoplasms
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on July 20, 2014