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

January 31, 2020 updated by: Amgen Research (Munich) GmbH

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 cluster of differentiation (CD)19 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.

Study Type

Interventional

Enrollment (Actual)

116

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • AMG 103
  • MT103
  • BLINCYTO™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
During the first cycle (6 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hematological Relapse-free Survival (RFS)
Time Frame: 18 months, up to the data cut-off date of 05 August 2015

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.
18 months, up to the data cut-off date of 05 August 2015
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.
Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
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.
100 days after HSCT, as of the data cut-off date of 05 August 2015
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).
Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
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.
Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
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.
Baseline and end of cycle 1 (6 weeks)
Number of Participants With Adverse Events
Time Frame: From the first dose of blinatumomab until 30 days after last dose; the median treatment duration was 55 days.

Adverse events (AEs) were evaluated for severity according to 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.
From the first dose of blinatumomab until 30 days after last dose; the median treatment duration was 55 days.
Change From Baseline in EORTC-QLQ-C30 Scales
Time Frame: Baseline and the end of each treatment cycle (day 29 of each cycle) and 30 days after end of the last infusion (end of the core study, a maximum of 26 weeks).

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (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 the change from baseline to the end of the core study are reported.
Baseline and the end of each treatment cycle (day 29 of each cycle) and 30 days after end of the last infusion (end of the core study, a maximum of 26 weeks).
Change From Baseline in EuroQoL 5-Dimension (EQ-5D) Scales
Time Frame: Baseline and the end of each treatment cycle (day 29 of each cycle) and 30 days after end of the last infusion (end of the core study, a maximum of 26 weeks).
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 the core study. The maximum observed change from baseline during cycles 1 to 4 and the change from baseline at the end of the core study are reported for each dimension.
Baseline and the end of each treatment cycle (day 29 of each cycle) and 30 days after end of the last infusion (end of the core study, a maximum of 26 weeks).
Resource Utilization: Number of Participants Reporting Use of Transfusion of Blood Products
Time Frame: From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months
From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months
Resource Utilization: Duration of Hospitalization
Time Frame: From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months.
From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen Research (Munich) GmbH

Investigators

  • Principal Investigator: Ralf Bargou, MD, Medizinische Klinik und Poliklinik II, Würzburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (ACTUAL)

February 1, 2014

Study Completion (ACTUAL)

January 7, 2019

Study Registration Dates

First Submitted

September 21, 2010

First Submitted That Met QC Criteria

September 21, 2010

First Posted (ESTIMATE)

September 22, 2010

Study Record Updates

Last Update Posted (ACTUAL)

February 10, 2020

Last Update Submitted That Met QC Criteria

January 31, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MT103-203

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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