DT388IL3 Fusion Protein in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes - Full Text View

Sponsored by:	Scott and White Hospital & Clinic
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00397579

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	Biological: DT(388)IL3 fusion protein Genetic: gene expression analysis Genetic: protein expression analysis Other: flow cytometry Other: immunoenzyme technique Other: laboratory biomarker analysis	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Dose-limiting toxicity [ Designated as safety issue: Yes ]
Toxicity profile [ Designated as safety issue: Yes ]
Maximum tolerated dose [ Designated as safety issue: Yes ]
Clinical response rate [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Anti-DT388IL3 antibodies at days 1, 15, and 30 [ Designated as safety issue: No ]
Serum DT388IL3 levels and half-life [ Designated as safety issue: No ]
Leukemia blast interleukin-3 receptor density at baseline [ Designated as safety issue: No ]
Acute myeloid leukemia (AML) progenitor sensitivity to DT388IL3 [ Designated as safety issue: No ]
Correlation of response to treatment with disease type (relapsed/refractory or poor-risk de novo AML or high-risk myelodysplastic syndromes) [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	July 2006
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

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

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

Locations

United States, North Carolina
Duke Comprehensive Cancer Center	Recruiting
Durham, North Carolina, United States, 27710
Contact: Clinical Trials Office - Duke Comprehensive Cancer Center 888-275-3853
United States, Texas
M. D. Anderson Cancer Center at University of Texas	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245
Scott and White Cancer Institute	Recruiting
Temple, Texas, United States, 76502
Contact: Arthur E. Frankel, MD 254-724-0094
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre	Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Donna E. Hogge, MD 604-875-4863

Sponsors and Collaborators

Scott and White Hospital & Clinic

Investigators

Study Chair:

Arthur E. Frankel, MD

Scott and White Hospital & Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Scott and White Cancer Institute ( Arthur E. Frankel )
Study ID Numbers:	CDR0000511032, S-WHITE-22304, S-WHITE-050047
Study First Received:	November 8, 2006
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00397579 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Recurrence
Leukemia

Preleukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Congenital Abnormalities
Bone Marrow Diseases

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Disease
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Leukemia
Preleukemia
Neoplasms
Pathologic Processes
Syndrome
Bone Marrow Diseases

ClinicalTrials.gov processed this record on September 01, 2009