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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.
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH Identifier:
First received: September 21, 2010
Last updated: March 30, 2017
Last verified: March 2017
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: Intervention Model: Single Group Assignment
Masking: No masking
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) ]

    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 (RFS) [ Time Frame: 18 months ]

    Hematological RFS was measured from first dose of blinatumomab until the first assessment of documented relapse (either hematological or extramedullary), secondary leukemia, or death due to any cause. Participants without a documented relapse, or death due to any cause were censored at the time of their last hematological assessment. Participants who received chemotherapy for relapsed or persistent MRD or for any other reason after treatment with blinatumomab, or HSCT after treatment with blinatumomab, before hematological or extramedullary relapse, or death occurred were censored at the start of chemotherapy or HSCT, respectively.

    Hematological relapse was defined as unequivocal detection of > 5% leukemia cells in bone marrow as measured by cytological, microscopic assessment, presence of circulating leukemia blasts, or extramedullary leukemia (whichever occurred first).

    The 18-month Kaplan-Meier estimate of hematological RFS is reported.

  • Overall Survival [ Time Frame: Until the data cut-off date of 05 August 2015; median time on study was 18.3 months. ]
    Overall survival was measured from the first treatment with blinatumomab until death due to any cause. Participants who did not die were censored at their last contact date.

  • 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant [ Time Frame: 100 days after HSCT, as of the data cut-off date of 05 August 2015 ]
    The mortality rate within 100 days after allogeneic HSCT was defined as the Kaplan-Meier estimate of the percentage of participants dying within 100 days after the day of the first allogeneic HSCT.

  • Time to Hematological Relapse [ Time Frame: Until the data cut-off date of 05 August 2015; median time on study was 18.3 months. ]
    Time to hematological relapse was measured from the start of treatment with blinatumomab until hematological or extramedullary relapse. Participants who died or received HSCT or post-blinatumomab chemotherapy after treatment with blinatumomab were censored at their last hematological assessment prior to death or HSCT or post-blinatumomab chemotherapy (whichever occurred first).

  • Duration of Complete MRD Response [ Time Frame: Until the data cut-off date of 05 August 2015; median time on study was 18.3 months. ]

    The duration of MRD response was analyzed as the time from onset of MRD negativity until MRD or hematological relapse or date of last confirmation of negative MRD status. Participants who received chemotherapy or HSCT after treatment with blinatumomab, before hematological or extramedullary relapse were censored at the start of chemotherapy or HSCT, respectively.

    MRD relapse is defined as the reappearance of individual rearrangements of Ig- or TCR-genes ≥ lower limit of quantification (LLOQ) for at least 1 individual marker measured by an assay with a sensitivity of minimum 10^-4. Hematological relapse is defined as the unequivocal detection of > 5% leukemia cells in bone marrow as measured by cytological or microscopic assessment, presence of circulating leukemia blasts, or extramedullary leukemia.

  • Change in MRD Level From Baseline to End of Cycle 1 in Non-MRD Responders [ Time Frame: Baseline and end of cycle 1 (6 weeks) ]
    MRD level was measured by polymerase chain reaction (PCR) performed on bone marrow and assessed by the central laboratory. An MRD level of 10^-n corresponds to residual leukemia cells at a frequency of 1 per 10ⁿ bone marrow cells.

  • Number of Participants With Adverse Events [ Time Frame: From the first dose of blinatumomab until 30 days after last dose. Adverse events are reported up to the data cut-off date of 05 August 2015; the median treatment duration was 55 days. ]

    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.

  • Change From Baseline in EORTC-QLQ-C30 Scales [ Time Frame: Subjects are assessed at Screening Visit (Baseline), at day 29 of each treatment cycle, at Day 30 Safety Follow-Up Visit and during mandated Efficacy Follow-Up Visits occurring at month 3, 6, 9, 12, 18 and 24 after treatment start. ]

    The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Insomnia, Appetite Loss, Constipation, Diarrhea, Financial Impact).

    For each of these scales, scores range from 0 to 100. For the GHS and 5 functional scales a high score indicates better global health status/functioning and a positive change from baseline indicates improvement. For the 9 symptom scales, a high score indicates a higher level of symptoms, and a negative change from Baseline indicates an improvement in symptoms.

    The maximum changes from baseline to cycles 1 through 4 and to the end of the core study are reported.

  • Change From Baseline in EuroQoL 5-Dimension (EQ-5D) Scales [ Time Frame: Subjects are assessed at Screening Visit (Baseline), at day 29 of each treatment cycle, at Day 30 Safety Follow-Up Visit and during mandated Efficacy Follow-Up Visits occurring at month 3, 6, 9, 12, 18 and 24 after treatment start. ]
    The EQ-5D is a self-administered questionnaire which captures 3 basic types of information: a descriptive profile (health state index) and the overall health rating using a visual analog scale. The health state index measures mobility, self-care, usual activities, pain/discomfort and anxiety/depression on scales from no problems (score = 1), some problems (score = 2), to extreme problems (score = 3). For each dimension the mean change from baseline was calculated at the end of each treatment cycle and at the end of study. The maximum observed change from baseline during cycles 1 to 4 and the change from baseline at the end of study are reported for each dimension.

  • Resource Utilization [ Time Frame: 5 years ]

Enrollment: 116
Study Start Date: November 2010
Estimated Study Completion Date: January 2019
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

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 occur until 24 months after treatment start. Participants will be followed for up to 5 years after the start of treatment for survival.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 identifier: NCT01207388

  Hide Study Locations
1102 - LKH Graz
Graz, Austria
1107 - Krankenhaus der Elisabethinen
Linz, Austria
Salzburg, Austria
1101 - AKH Wien
Vienna, Austria
Antwerpen, Belgium
1502 - Cliniques Universitaires de Saint-Luc
Brussels, Belgium
Brügge, Belgium
Gent, Belgium
1501 - Cliniques Universitaires UCL de Mont Godinne
Yvoir, Belgium
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
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
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
2204 - UMC Groningen
Groningen, Netherlands
2201 - Daniel Den Hoed Hospitaal
Rotterdam, Netherlands
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
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
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
Principal Investigator: Ralf Bargou, MD Medizinische Klinik und Poliklinik II, Würzburg
Principal Investigator: Nicola Gökbuget, MD Klinikum der Goethe Universität Frankfurt
  More Information

Responsible Party: Amgen Research (Munich) GmbH 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: March 30, 2017

Keywords provided by Amgen Research (Munich) GmbH:
Minimal residual disease
adult ALL
Lymphatic diseases
Lymphoproliferative disorders
bispecific antibody
Immunotherapeutic treatment

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasm, Residual
Burkitt Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Antibodies, Bispecific
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on May 23, 2017