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LeukemiaPhase 1/2NCT00397579

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

A Phase 1/2 study testing DT388IL3 in people with Leukemia and Myelodysplastic Syndromes, run by University of Texas Southwestern Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
DT388IL3
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
May 2013to 27 Jul 2017
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
DT388IL3
Keywords
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+
Medical subject headings
Leukemia, Myelodysplastic Syndromes, Blastic Plasmacytoid Dendritic Cell Neoplasm, Congenital Abnormalities, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DT388IL3Drug

    Intravenously via a 3 cc plastic syringe as a 15 minute bolus infusion daily for five days.

Study groups in NCT00397579
Study groupRoleWhat they receive
SL-401ExperimentalPatients 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.
Receives: Drug: DT388IL3

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (CR+PR+SD): Percentage of Participants Experiencing Response

    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:

    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.

    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.

    Stable Disease (SD); failure to achieve at least PR, and there is no evidence of progression for 2 months.

    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.

    Reported is the percentage of participants experiencing either CR, PR or SD.

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2006 (estimated)
  2. Study startMay 2013
  3. Primary completion27 Jul 2017
  4. Study completion27 Jul 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00397579
Sponsor's protocol ID
STU 012013-061
Status last verified
Mar 2019
First submitted
8 Nov 2006
Last updated
23 Apr 2019
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24859366

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing DT388IL3 in people with Leukemia and Myelodysplastic Syndromes, run by University of Texas Southwestern Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (CR+PR+SD): Percentage of Participants Experiencing Response (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00397579, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2019.

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