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
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes, Blastic Plasmacytoid Dendritic Cell Neoplasm, Plasmacytoid Dendritic Cell Leukemia
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 Institute | Temple, Texas 76508 |
