Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT01466179
First received: October 28, 2011
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to confirm whether the bispecific T cell engager antibody blinatumomab (MT103) is effective and safe in the treatment of patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL).


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Blinatumomab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter, Phase II Study to Evaluate Efficacy and Safety of the BiTE Antibody Blinatumomab in Adult 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:
  • CR + CRh* rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
    rate of complete remission and complete remission with partial hematologic recovery within in the first two treatment cycles


Secondary Outcome Measures:
  • Proportion of patients eligible for allogeneic hematopoietic stem cell transplantation (HSCT) who undergo the procedure after treatment with blinatumomab [ Time Frame: within 17 months ] [ Designated as safety issue: No ]
  • CR rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
  • CRh* rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
  • Partial remission (PR) rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
  • Relapse-free survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Number of AEs per patient [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]
  • 100-day mortality after allogeneic HSCT [ Time Frame: within 4 years ] [ Designated as safety issue: Yes ]
  • Steady state concentration of blinatumomab (pharmacokinetics) [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
  • Serum cytokine concentrations [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
  • Rate of MRD response [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
  • Rate of MRD complete response [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
  • Time to hematological relapse [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
  • Concentration of peripheral blood lymphocyte subsets [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 180
Study Start Date: November 2011
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Blinatumomab
Bispecific T cell engager antibody
Drug: Blinatumomab
continuous intravenous infusion over four weeks per treatment cycle
Other Names:
  • AMG103
  • MT103

Detailed Description:

Relapsed/refractory B-precursor ALL in adult patients is an aggressive malignant disease with dismal prog-nosis. Several studies have reported long term survival to be below 10%. Major prognostic factors are duration of first complete remission (CR1) and age. With current salvage chemotherapy, complete remission (CR) rate is low (20 to 30%) in patients in first salvage with short duration (< one year) of first remission, patients relapsed after first salvage, or patients aged 60 years and older. Duration of CR is usually very short (median disease free survival [DFS]: 2.0-7.5 months). Allogeneic hematopoietic stem cell transplantation (HSCT) may provide a curative treatment option for patients in CR with a satisfactory donor and appropriate clinical status including age, organ function, and remission status. Allogeneic HSCT is not an option in most elderly patients with relapsed ALL. Additional therapeutic approaches are urgently needed.

Blinatumomab (also termed MT 103) is a bispecific single-chain antibody derivative against CD (cluster of differentiation)19 and CD3, designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. In vitro data indicate CD19+ lymphoma and leukemia cell lines to be extremely sensitive to blinatumomab-mediated cytotoxicity.Blinatumomab has the potential to provide meaningful therapeutic benefits to patients compared with existing treatments for this patient population.

The purpose of this study is to confirm whether the bispecific T-cell engager blinatumomab (MT103) is effective and safe in the treatment of patients with relapsed or refractory ALL. Patients will receive up to five 4-week cycles of intravenous blinatumomab treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with Ph-negative B-precursor ALL, with any of the following:
  • relapsed or refractory with first remission duration less than or equal to 12 months in first salvage or
  • relapsed or refractory after first salvage therapy or
  • relapsed or refractory within 12 months of allogeneic HSCT
  • 10% or more blasts in bone marrow
  • In case of clinical signs of additional extramedullary disease: measurable disease
  • ECOG performance status ≤ 2
  • Age ≥ 18 years

Exclusion Criteria:

  • Patients with Ph-positive ALL
  • Patients with Burkitt's Leukemia according to WHO classification
  • History or presence of clinically relevant CNS pathology
  • Active ALL in the CNS or testes
  • Current autoimmune disease or history of autoimmune disease with potential CNS involvement
  • Autologous HSCT within six weeks prior to start of blinatumomab treatment
  • Allogeneic HSCT within three months prior to start of blinatumomab treatment
  • Any active acute GvHD, or active chronic GvHD Grade 2 - 4
  • Any systemic therapy against GvHD within two weeks prior to start of blinatumomab treatment
  • Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
  • Radiotherapy within two weeks prior to start of blinatumomab treatment
  • Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treat-ment
  • Any investigational anti-leukemic product within four weeks prior to start of blinatumomab treatment
  • Treatment with any other IMP after signature of informed consent
  • Eligibility for allogeneic HSCT at the time of enrollment
  • Known hypersensitivity to immunoglobulins or to any other component of the IMP formulation
  • Abnormal laboratory values indicative of inadequate renal or liver function
  • History of malignancy requiring treatment other than ALL within five years prior to start of blinatumomab treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
  • Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study
  • Infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus
  • Pregnant or nursing women
  • Women of childbearing potential not willing to use an effective form of contraception. Male patients not willing to ensure not to beget a child
  • Previous treatment with blinatumomab
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01466179

  Hide Study Locations
Locations
United States, California
City of Hope
Duarte, California, United States, 91010-3000
University of California Los Angeles
Los Angeles, California, United States, 90095-1678
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Massachusetts
Dana Farber Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Streets
Buffalo, New York, United States, 14263
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
France
CHU d'Angers
Angers, France, 49933
Hôpital de l'hôtel Dieu
Nantes, France, 44000
Hôpital Saint Louis
Paris, France, 75475
CHU de Purpan
Toulouse, France, 31059
Germany
Charité - Campus Benjamin Franklin
Berlin, Germany, 12200
Klinikum der Goethe Universität, Medizinische Klinik II
Frankfurt, Germany, 60590
Universitätsklinikum Freiburg
Freiburg, Germany, 79106
Medizinische Hochschule Hannover
Hannover, Germany, 30625
Universitätsklinikum Schleswig-Holstein
Kiel, Germany, 24116
Universitätsklinikum Münster
Münster, Germany, 48149
Universitätsklinikum Tübingen
Tübingen, Germany, 72076
Universitätsklinikum Ulm
Ulm, Germany, 89081
Julius-Maximilians-Universität, Medizinische Klinik und Poliklinik II
Würzburg, Germany, 97080
Italy
Ospedali Riuniti di Bergamo
Bergamo, Italy, 24128
Azienda Ospedaliera Antonio Cardarelli
Naples, Italy, 80131
Ospedali Riuniti "Villa Sofia-Cervello"
Palermo, Italy, 90146
Università La Sapienza di Roma
Rome, Italy, 00161
Azienda Ospedaliero-Universitaria
Turin, Italy, 10126
Azienda Ospedaliera di Verona
Verona, Italy, 37134
Spain
ICO Hospital Germans Trias I Pujol
Badalona, Spain, 08916
Hospital Clínic Servei d´Hematologia
Barcelona, Spain, 08036
Hospital 12 de Octubre
Madrid, Spain, 28041
Hospital universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitario Virgen Del Rocio
Sevilla, Spain, 41013
United Kingdom
University Hospitals Bristol NHS
Bristol, United Kingdom, BS2 8ED
Royal Free Hampstead NHS Trust
London, United Kingdom, NW3 2QG
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Amgen Research (Munich) GmbH
Investigators
Principal Investigator: Nicola Gökbuget, MD Klinikum der Goethe Universität Frankfurt
Principal Investigator: Max Topp, MD Julius-Maximilians-Universität, Medizinische Klinik und Poliklinik II, Würzburg
Principal Investigator: Hagop Kantarjian, MD MD Anderson Cancer Center, Houston, Texas
  More Information

No publications provided

Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01466179     History of Changes
Other Study ID Numbers: MT103-211, 2011-002257-61
Study First Received: October 28, 2011
Last Updated: November 20, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ethics Committee
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Amgen Research (Munich) GmbH:
B-ALL
relapsed ALL
refractory ALL
adult ALL
Leukemia
Leukemia, Lymphoid
precursor cell lymphoblastic leukemia-lymphoma
Lymphatic diseases
Lymphoproliferative disorders
bispecific antibody
anti-CD19
Immunotherapeutic treatment
immunoproliferative disorders

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
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014