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

NCT00397579 | Completed Phase 1 Results DMC

• 1 other identifier: STU 012013-061
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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 myeloid leukemia or myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes; Blastic Plasmacytoid Dendritic Cell Neoplasm

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+

Outcome Measures

Primary Outcomes (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.

  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

Study Arms (1)

SL-401

EXPERIMENTAL

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.

Drug: DT388IL3

Interventions

DT388IL3 DRUG

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

SL-401

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• 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.

  PMID: 24859366 DERIVED

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Blastic Plasmacytoid Dendritic Cell Neoplasm; Congenital Abnormalities; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid

Results Point of Contact

• Title: Clinical Research Office
• Organization: University of Texas Southwestern Medical Center at Dallas

studyfinder@utsouthwestern.edu

214-648-7097

Study Officials

• Arthur E. Frankel, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2006
• First Posted: November 9, 2006
• Study Start: May 1, 2013
• Primary Completion: July 27, 2017
• Study Completion: July 27, 2017
• Last Updated: April 23, 2019
• Results First Posted: April 23, 2019

Record last verified: 2019-03

Locations

US (1)