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Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

This study has been completed.
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH Identifier:
First received: October 28, 2011
Last updated: July 12, 2016
Last verified: July 2016
The purpose of this study is to determine the dose of the bispecific T cell engager blinatumomab (MT103) in pediatric and adolescent patients with relapsed/refractory Acute Lymphoblastic Leukemia (ALL) and to assess whether this dose of blinatumomab is effective.

Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: blinatumomab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Arm Multicenter Phase II Study Preceded by Dose Evaluation to Investigate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab (MT103) in Pediatric and Adolescent Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:

Further study details as provided by Amgen Research (Munich) GmbH:

Primary Outcome Measures:
  • Phase I part: Maximal tolerable dose [ Time Frame: within 2 years ] [ Designated as safety issue: Yes ]
    Maximal tolerable dose defined by <= 1 of 6 patients experiencing dose limiting toxicity or maximal administered dose

  • Phase II part: Rate of complete remission (CR) [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall incidence and severity of adverse events [ Time Frame: within 3 years ] [ Designated as safety issue: Yes ]
  • Proportion of patients who undergo allogeneic HSCT after treatment with blinatumomab [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • CR duration [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • Steady state concentration of blinatumomab (pharmacokinetics) [ Time Frame: within 2 years ] [ Designated as safety issue: No ]
  • Cytokine serum concentrations [ Time Frame: within 2 years ] [ Designated as safety issue: Yes ]
  • Time to hematological relapse [ Time Frame: within 2 years ] [ Designated as safety issue: No ]

Enrollment: 93
Study Start Date: January 2012
Study Completion Date: May 2016
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: blinatumomab Drug: blinatumomab
intravenous infusion
Other Names:
  • MT103
  • AMG103

Detailed Description:
Relapsed/refractory B-precursor ALL in pediatric and adolescent patients is an aggressive malignant disease with dismal prognosis. Apart from allogeneic hematological stem cell transplantation (HSCT) there is not any other curative treatment of second relapse or refractory B-precursor ALL available. Additional therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. The purpose of this study is to investigate the pharmacokinetics, pharmacodynamics and safety of escalating doses of the BiTE® antibody blinatumomab (MT103)in pediatric and adolescent patients with relapsed/refractory B-precursor ALL, to select a dose and to investigate the efficacy and safety of that dose of blinatumomab in above mentioned patient population. Patients will receive up to five 6-weeks cycles (4 weeks of continuous intravenous infusion followed by a 2-weeks treatment free interval) of blinatumomab treatment.

Ages Eligible for Study:   up to 17 Years   (Child)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Morphologic evidence of B-precursor ALL with > 25% blasts in bone marrow (M3)at study enrolment
  • Age less than 18 years at enrollment
  • Relapsed/refractory disease:

    • Second or later bone marrow relapse,
    • Any marrow relapse after allogeneic HSCT, or
    • Refractory to other treatments: Patients in first relapse must have failed to achieve a CR following full standard reinduction chemotherapy regimen of at least 4 weeks duration.Patients who have not achieved a first remission must have failed a full standard induction regimen
  • Karnofsky performance status more than or equal to 50% for patients more than or equal to 16 years and Lansky Performance Status (LPS) of more than or equal to 50% for patients less than 16 years
  • Organ function requirements: All patients must have adequate renal and liver functions

Exclusion Criteria:

  • Active acute or extensive chronic GvHD
  • Immunosuppressive agents to prevent or treat GvHD within 2 weeks prior to blinatumomab treatment
  • Evidence for current CNS involvement by ALL (CNS 2, CNS 3) or testicular involvement by ALL
  • History of relevant CNS pathology or current relevant CNS pathology
  • History of autoimmune disease with potential CNS involvement or current autoimmune disease
  • Any HSCT within 3 months prior to blinatumomab treatment
  • Cancer chemotherapy within 2 weeks prior to blinatumomab treatment (except for intrathecal chemotherapy and/or low dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, glucocorticoids)
  • Chemotherapy related toxicities that haven't resolved to less than or equal to Grade 2
  • Radiotherapy within 2 weeks prior to blinatumomab treatment
  • Immunotherapy (e.g. rituximab, alemtuzumab) within 6 weeks prior to blinatumomab treatment
  • Any investigational product within 4 weeks prior to study entry
  • Previous treatment with blinatumomab
  • Active severe infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
  • Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01471782

  Hide Study Locations
United States, Colorado
Children's Hospital Denver
Aurora, Colorado, United States, 80045
United States, Georgia
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, United States, 30322
United States, Missouri
Washington University
ST. Louis, Missouri, United States
United States, New York
Memorial Sloan Kettering
New York, New York, United States, 10065
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105-3678
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390-9063
Texas Children's Cancer Center/ Baylor
Houston, Texas, United States, 77030-2399
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
St. Anna Kinderspital
Vienna, Austria, 1090
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G1X8
(CHU Besancon) Hopital Saint-Jaques
Besancon, France, 25030
Hôpital de la Timone (Enfants)
Marseille, France
Hopital Robert Debré (AP-HP)
Paris Cedex 19, France, 75935
Charité Campus Virchow Klinikum, Otto-Heubner-Centrum (OHC) für Kinder- und Jugendmedizin
Berlin, Germany, 13353
Universitätsklinikum Düsseldorf
Düsseldorf, Germany, 40225
Universitätsklinikum Essen
Essen, Germany
Klinikum der Johann Wolfgang Goethe-Universität Frankfurt/Main
Frankfurt am Main, Germany, 60590
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany
Medizinische Hochschule Hannover
Hannover, Germany
Universitätsklinikum Schleswig-Holstein Campus Kiel
Kiel, Germany
Klinikum der Universität München, Dr. von Haunersches Kinderspital
München, Germany, 80337
Universitätsklinik für Kinder- und Jugendmedizin Tübingen
Tübingen, Germany, 72076
Universitätsklinikum Würzburg
Würzburg, Germany
University of Milano-Bicocca, Hospital San Gerardo
Monza, Italy, 20052
Dipartimento della Donna e del Bambino
Padova, Italy
The Bambino Gesù Children's Hospital
Rome, Italy, 00165
Erasmus MC, Sophia Children's Hospital
Rotterdam, Netherlands, 3015 GJ
Sponsors and Collaborators
Amgen Research (Munich) GmbH
Study Chair: Arend von Stackelberg, MD Charité Campus Virchow Klinikum
Study Chair: Lia Gore, MD Children's Hospital Denver, USA
  More Information

Responsible Party: Amgen Research (Munich) GmbH Identifier: NCT01471782     History of Changes
Other Study ID Numbers: MT103-205  2010-024264-18 
Study First Received: October 28, 2011
Last Updated: July 12, 2016
Health Authority: Germany: Paul-Ehrlich-Institut
United States: Food and Drug Administration

Keywords provided by Amgen Research (Munich) GmbH:
relapsed, refractory B-precursor ALL
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Antibodies, Bispecific

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Bispecific
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on January 14, 2017