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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT01471782
First received: October 28, 2011
Last updated: July 3, 2014
Last verified: November 2013
  Purpose

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 ]

Estimated Enrollment: 84
Study Start Date: January 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: October 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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT01471782

  Show 30 Study Locations
Sponsors and Collaborators
Amgen Research (Munich) GmbH
Investigators
Study Chair: Arend von Stackelberg, MD Charité Campus Virchow Klinikum
Study Chair: Lia Gore, MD Children's Hospital Denver, USA
  More Information

No publications provided

Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01471782     History of Changes
Other Study ID Numbers: MT103-205, 2010-024264-18
Study First Received: October 28, 2011
Last Updated: July 3, 2014
Health Authority: Germany: Paul-Ehrlich-Institut
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014