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Trial record 7 of 15 for:    Blastic plasmacytoid dendritic cell neoplasm

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

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ClinicalTrials.gov Identifier: NCT00397579
Recruitment Status : Completed
First Posted : November 9, 2006
Last Update Posted : May 10, 2018
Sponsor:
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

November 8, 2006
November 9, 2006
May 10, 2018
May 2013
July 27, 2017   (Final data collection date for primary outcome measure)
Response Measurements [ Time Frame: treated over a 10 day period ]
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.
  • Dose-limiting toxicity
  • Toxicity profile
  • Maximum tolerated dose
  • Clinical response rate
  • Duration of response
  • Anti-DT388IL3 antibodies at days 1, 15, and 30
  • Serum DT388IL3 levels and half-life
  • Blast cell gene expression at baseline
  • Leukemia blast interleukin (IL)-3 receptor density at baseline
  • Acute myeloid leukemia (AML) progenitor sensitivity to DT388IL3
  • AML type (relapsed/refractory vs poor risk-de novo)
Complete list of historical versions of study NCT00397579 on ClinicalTrials.gov Archive Site
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DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
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

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.

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.

Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Leukemia
  • Myelodysplastic Syndromes
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
Drug: DT388IL3
Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.
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.
Intervention: Drug: DT388IL3
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
50
July 27, 2017
July 27, 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
Canada
 
NCT00397579
STU 012013-061
Yes
Not Provided
Not Provided
University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center
Not Provided
Principal Investigator: Arthur E. Frankel, MD UT Southwestern Medical Center
University of Texas Southwestern Medical Center
May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP