Confirmatory Phase II Study of Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia (ALL) (BLAST)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT01207388
First received: September 21, 2010
Last updated: January 28, 2015
Last verified: January 2014
  Purpose

The purpose of this study is to confirm whether the bispecific T cell engager blinatumomab (MT103) is effective, safe and tolerable in the treatment of ALL patients with minimal residual disease.


Condition Intervention Phase
B-cell Acute Lymphoblastic Leukemia
Drug: Blinatumomab
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 Confirmatory Multicenter, Single-arm Study to Assess the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Minimal Residual Disease (MRD) of B-precursor Acute Lymphoblastic Leukemia (BLAST)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Percentage of Participants With a Minimal Residual Disease (MRD) Response Within the First Treatment Cycle [ Time Frame: During the first cycle (6 weeks) ] [ Designated as safety issue: No ]

    At the end of the first treatment cycle (Day 29) a bone marrow aspiration/biopsy was performed and evaluated by the central MRD laboratory.

    Complete MRD response is defined as no polymerase chain reaction (PCR) amplification of individual rearrangements of immunoglobulin (Ig)- or T-cell receptor (TCR)-genes detected after completion of the first cycle.



Secondary Outcome Measures:
  • Hematological Relapse-free Survival Rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant [ Time Frame: 100 days after HSCT ] [ Designated as safety issue: No ]
  • Time to Hematological Relapse [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Duration of Complete MRD Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • MRD Level [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events [ Time Frame: Adverse events are reported until the data cut-off date of 21 February 2014; the median treatment duration was 52 days. ] [ Designated as safety issue: Yes ]

    Adverse events (AEs) were evaluated for severity according to the the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4, as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death.

    The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab.

    An AE was considered "serious" if it resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions, was a congenital anomaly or birth defect or was a medically important condition.


  • Quality of Life [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Resource Utilization [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 116
Study Start Date: November 2010
Estimated Study Completion Date: August 2016
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Blinatumomab
Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate of 15 μg/m²/day over 28 days followed by an infusion-free period of 14 days for up to 4 cycles of treatment.
Drug: Blinatumomab
Continuous intravenous infusion
Other Names:
  • AMG103
  • MT103
  • BLINCYTO™

Detailed Description:

The detection of minimal residual disease (MRD) after induction therapy and/or consolidation therapy is an independent prognostic factor for poor outcome of adult ALL. No standard treatments are available for patients with MRD-positive B-precursor ALL. Blinatumomab (MT103) 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 confirm whether the bispecific T-cell engager blinatumomab (MT103) is effective, safe and tolerable in the treatment of ALL patients with minimal residual disease.

Participants will receive up to four 4-week cycles of intravenous blinatumomab treatment followed by an infusion-free period of 14 days. A safety follow-up will be performed 30 days after the end of the last infusion and efficacy follow-ups will occurr until 24 months after treatment start. Participants will be followed for up to 5 years after the start of treatment for survival.

  Eligibility

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

Inclusion Criteria:

  • Patients with B-precursor ALL in complete hematological remission after at least 3 intense chemotherapy blocks
  • Presence of minimal residual disease at a level of ≥ 10^-3
  • Availability of bone marrow specimen from primary diagnosis for clone-specific MRD assessment
  • Negative human immunodeficiency virus (HIV) test, negative hepatitis B (HbsAg) test and hepatitis C virus (anti-HCV) test
  • Negative pregnancy test in women of childbearing potential
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

  • Presence of circulating blasts or current extra-medullary involvement by ALL
  • History of relevant central nervous system (CNS) pathology or current CNS pathology
  • Prior allogeneic hematopoietic stem cell transplant (HSCT)
  • Eligibility for treatment with tyrosine-kinase inhibitors (TKI)
  • Systemic cancer chemotherapy within 2 weeks prior to study treatment
  • Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment
  • Previous treatment with blinatumomab
  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: NCT01207388

  Hide Study Locations
Locations
Austria
1102 - LKH Graz
Graz, Austria
1107 - Krankenhaus der Elisabethinen
Linz, Austria
1106
Salzburg, Austria
1101 - AKH Wien
Vienna, Austria
Belgium
1504
Antwerpen, Belgium
1502 - Cliniques Universitaires de Saint-Luc
Brussels, Belgium
1505
Brügge, Belgium
1503
Gent, Belgium
1501 - Cliniques Universitaires UCL de Mont Godinne
Yvoir, Belgium
France
1211 - CHU d'Angers
Angers, France
1210 - CHU de Besançon
Besançon, France
1206 - Hôpital de Pontoise
Cergy Pontoise, France
1205 - CHU Henri Mondor
Créteil, France
1209 - CHU de Lyon
Lyon, France
1212 - Hôpital de l'hôtel Dieu
Nantes, France
1213 - Centre Hospitalier Universitaire de Nice
Nice, France
1201 - Hôpital Saint Louis
Paris, France
1202 - CHU de Bordeaux - Hôpital Haut Lévêque
Pessac, France
1208 - CHU de Purpan
Toulouse, France
Germany
1011 - Charité Berlin
Berlin, Germany
1022 - Universitätsklinkum Carl Gustav Carus Dresden
Dresden, Germany
1009 - Universitätsklinikum Essen
Essen, Germany
1002 - Klinikum der Goethe Universität
Frankfurt, Germany
1014 - Asklepiosklinik St. Georg
Hamburg, Germany
1018 - Medizinische Hochschule Hannover
Hannover, Germany
1012 - Universitätsklinikum Heidelberg
Heidelberg, Germany
1003 - Universitätsklinikum Schleswig-Holstein
Kiel, Germany
1019 - Universitätsklinikum Leipzig
Leipzig, Germany
1010 - Klinikum der Universität München - Großhadern
Munich, Germany
1004 - Universitätsklinikum Münster
Münster, Germany
1016 - Universitätsklinikum Regensburg
Regensburg, Germany
1020 - Universitätsklinikum Rostock
Rostock, Germany
1007 - Robert-Bosch-Krankenhaus
Stuttgart, Germany
1015 - Universitätsklinikum Tübingen
Tübingen, Germany
1005 - Universitätsklinikum Ulm
Ulm, Germany
1001 - Julius-Maximilians-Universität Würzburg
Würzburg, Germany
Italy
1301 - Ospedali Riuniti di Bergamo
Bergamo, Italy
1303 - Istituto di Ematologia "L.& A.Seràgnoli" Azienda
Bologna, Italy
1314 - Azienda Ospedaliera Spedali Civili Brescia
Brescia, Italy
1313 - Universita di Catania
Catania, Italy
1312 - Azienda Ospedaliera Universitaria San Martino
Genoa, Italy
1305 - Ospedale San Gerardo
Monza, Italy
1309 - Azienda Ospedaliera Antonio Cardarelli
Napoli, Italy
1308 - Ospedali Riuniti "Villa Sofia-Cervello"
Palermo, Italy
1302 - Università La Sapienza di Roma
Rome, Italy
1310 - Fondazione Policlinico Tor Vergata
Rome, Italy
1315 - Azienda Ospedaliero-Universitaria S. Giovanni Battista (Le Molinette)
Torino, Italy
1311 - Azienda Ospedaliera di Verona
Verona, Italy
Netherlands
2204 - UMC Groningen
Groningen, Netherlands
2201 - Daniel Den Hoed Hospitaal
Rotterdam, Netherlands
Poland
1905 - Uniwersytecki Szpital Kliniczny w Białymstoku
Bialystok, Poland
1907 - Uniwersyteckie Centrum Kliniczne
Gdansk, Poland
1908 - Swietokrzyskie Centrum Onkologii
Kielce, Poland
1902 - Uniwersytet Medyczny w Lublinie
Lublin, Poland
1901 - Klinika Hematologii - Instytut Hematologii i Transfuzjologii
Warsaw, Poland
1906 - MTZ Clinical Research Sp. z o.o.
Warsaw, Poland
1904 - Samodzielny Publiczny
Wrocław, Poland
Romania
2101 - Institutul Clinic Fundeni, Hematologie II
Bucharest, Romania
2102 - Spitalul Clinic Coltea, Hematologie
Bucharest, Romania
2106 - Institutul Oncologic "Prof. Dr. I. Chiricuta"
Cluj-Napoca, Romania
2105 - Institutul Regional de Oncologie
Iasi, Romania
Russian Federation
2001 - Russian Hematology Research Center
Moscow, Russian Federation
2003 - Municipal Hospital No. 15
St. Petersburg, Russian Federation
Spain
1401 - ICO Hospital Germans Trias I Pujol
Badalona, Spain
1404 - Hospital Clínic Servei d´Hematologia
Barcelona, Spain
1402 - Complexo Hospitalario Universitario A Coruña
La Coruña, Spain
1408 - Hospital 12 de Octubre
Madrid, Spain
1405 - Hospital Universitari Son Espases
Mallorca, Spain
1407 - Unidad de Citogenética Oncológica
Salamanca, Spain
1406 - Hospital Universitari i Politècnic La Fe de Valencia
Valencia, Spain
United Kingdom
1605 - Queen Elizabeth Hospital
Birmingham, United Kingdom
1602 - Bristol Royal Infirmary
Bristol, United Kingdom
1604 - University Hospital of Wales
Cardiff, United Kingdom
1601 - Royal Free Hospital
London, United Kingdom
1607 - Nottingham City Hospital NHS Trust
Nottingham, United Kingdom
Sponsors and Collaborators
Amgen Research (Munich) GmbH
Investigators
Principal Investigator: Ralf Bargou, MD Medizinische Klinik und Poliklinik II, Würzburg
Principal Investigator: Nicola Gökbuget, MD Klinikum der Goethe Universität Frankfurt
  More Information

No publications provided

Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01207388     History of Changes
Other Study ID Numbers: MT103-203
Study First Received: September 21, 2010
Results First Received: January 28, 2015
Last Updated: January 28, 2015
Health Authority: Germany: Paul-Ehrlich-Institut
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Russia: Ministry of Health of the Russian Federation
Romania: National Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Amgen Research (Munich) GmbH:
Blinatumomab
MRD
B-ALL
Minimal residual disease
adult ALL
Leukemia
ALL
Lymphatic diseases
Lymphoproliferative disorders
bispecific antibody
anti-CD19
Immunotherapeutic treatment

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Neoplasm, Residual
Precursor Cell Lymphoblastic Leukemia-Lymphoma
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Neoplastic Processes
Pathologic Processes
Tumor Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 02, 2015