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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


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Myelodysplastic Syndromes, Blastic Plasmacytoid Dendritic Cell Neoplasm, Plasmacytoid Dendritic Cell Leukemia

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity

Safety Issue:

Yes

Principal Investigator

Arthur E. Frankel, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Scott and White Hospital & Clinic

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000511032

NCT ID:

NCT00397579

Start Date:

July 2006

Completion Date:

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Plasmacytoid Dendritic Cell Leukemia
  • 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+
  • Neoplasms
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

Scott and White Cancer InstituteTemple, Texas  76508