Clinical trial NCT01207388: Confirmatory Phase II Study of Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia (ALL)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-cell Acute Lymphoblastic Leukemia
Keywords: Blinatumomab
MRD
B-ALL
Minimal residual disease
adult ALL
Leukemia
ALL
Lymphatic diseases
Lymphoproliferative disorders
bispecific antibody
anti-CD19
Immunotherapeutic treatment
Lead sponsor: Amgen Research (Munich) GmbH
Sponsor class: INDUSTRY
First posted: 2010-09-22
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants With a Minimal Residual Disease (MRD) Response Within the First Treatment Cycle
timeFrame: During the first cycle (6 weeks)
Secondary outcomes:
measure: Hematological Relapse-free Survival (RFS)
timeFrame: 18 months, up to the data cut-off date of 05 August 2015
measure: Overall Survival
timeFrame: Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
measure: 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
timeFrame: 100 days after HSCT, as of the data cut-off date of 05 August 2015
measure: Time to Hematological Relapse
timeFrame: Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
measure: Duration of Complete MRD Response
timeFrame: Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.
measure: Change in MRD Level From Baseline to End of Cycle 1 in Non-MRD Responders
timeFrame: Baseline and end of cycle 1 (6 weeks)
measure: Number of Participants With Adverse Events
timeFrame: From the first dose of blinatumomab until 30 days after last dose; the median treatment duration was 55 days.
measure: Change From Baseline in EORTC-QLQ-C30 Scales
timeFrame: 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).
measure: Change From Baseline in EuroQoL 5-Dimension (EQ-5D) Scales
timeFrame: 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).
measure: Resource Utilization: Number of Participants Reporting Use of Transfusion of Blood Products
timeFrame: From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months
measure: Resource Utilization: Duration of Hospitalization
timeFrame: From first dose of study drug through the end of follow-up; median (minimum, maximum) time on study was 33.8 (1, 62) months.
Other outcomes:
Locations:
city: Graz
country: Austria
facility: 1102 - LKH Graz
city: Linz
country: Austria
facility: 1107 - Krankenhaus der Elisabethinen
city: Salzburg
country: Austria
facility: 1106
city: Vienna
country: Austria
facility: 1101 - AKH Wien
city: Antwerpen
country: Belgium
facility: 1504
city: Brussels
country: Belgium
facility: 1502 - Cliniques Universitaires de Saint-Luc
city: Brügge
country: Belgium
facility: 1505
city: Gent
country: Belgium
facility: 1503
city: Yvoir
country: Belgium
facility: 1501 - Cliniques Universitaires UCL de Mont Godinne
city: Angers
country: France
facility: 1211 - CHU d'Angers
city: Besançon
country: France
facility: 1210 - CHU de Besançon
city: Cergy Pontoise
country: France
facility: 1206 - Hôpital de Pontoise
city: Créteil
country: France
facility: 1205 - CHU Henri Mondor
city: Lyon
country: France
facility: 1209 - CHU de Lyon
city: Nantes
country: France
facility: 1212 - Hôpital de l'hôtel Dieu
city: Nice
country: France
facility: 1213 - Centre Hospitalier Universitaire de Nice
city: Paris
country: France
facility: 1201 - Hôpital Saint Louis
city: Pessac
country: France
facility: 1202 - CHU de Bordeaux - Hôpital Haut Lévêque
city: Toulouse
country: France
facility: 1208 - CHU de Purpan
city: Berlin
country: Germany
facility: 1011 - Charité Berlin
city: Dresden
country: Germany
facility: 1022 - Universitätsklinkum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: 1009 - Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: 1002 - Klinikum der Goethe Universität
city: Hamburg
country: Germany
facility: 1014 - Asklepiosklinik St. Georg
city: Hannover
country: Germany
facility: 1018 - Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: 1012 - Universitätsklinikum Heidelberg
city: Kiel
country: Germany
facility: 1003 - Universitätsklinikum Schleswig-Holstein
city: Leipzig
country: Germany
facility: 1019 - Universitätsklinikum Leipzig
city: Munich
country: Germany
facility: 1010 - Klinikum der Universität München - Großhadern
city: Münster
country: Germany
facility: 1004 - Universitätsklinikum Münster
city: Regensburg
country: Germany
facility: 1016 - Universitätsklinikum Regensburg
city: Rostock
country: Germany
facility: 1020 - Universitätsklinikum Rostock
city: Stuttgart
country: Germany
facility: 1007 - Robert-Bosch-Krankenhaus
city: Tübingen
country: Germany
facility: 1015 - Universitätsklinikum Tübingen
city: Ulm
country: Germany
facility: 1005 - Universitätsklinikum Ulm
city: Würzburg
country: Germany
facility: 1001 - Julius-Maximilians-Universität Würzburg
city: Bergamo
country: Italy
facility: 1301 - Ospedali Riuniti di Bergamo
city: Bologna
country: Italy
facility: 1303 - Istituto di Ematologia "L.& A.Seràgnoli" Azienda
city: Brescia
country: Italy
facility: 1314 - Azienda Ospedaliera Spedali Civili Brescia
city: Catania
country: Italy
facility: 1313 - Universita di Catania
city: Genoa
country: Italy
facility: 1312 - Azienda Ospedaliera Universitaria San Martino
city: Monza
country: Italy
facility: 1305 - Ospedale San Gerardo
city: Napoli
country: Italy
facility: 1309 - Azienda Ospedaliera Antonio Cardarelli
city: Palermo
country: Italy
facility: 1308 - Ospedali Riuniti "Villa Sofia-Cervello"
city: Rome
country: Italy
facility: 1302 - Università La Sapienza di Roma
city: Rome
country: Italy
facility: 1310 - Fondazione Policlinico Tor Vergata
city: Torino
country: Italy
facility: 1315 - Azienda Ospedaliero-Universitaria S. Giovanni Battista (Le Molinette)
city: Verona
country: Italy
facility: 1311 - Azienda Ospedaliera di Verona
city: Groningen
country: Netherlands
facility: 2204 - UMC Groningen
city: Rotterdam
country: Netherlands
facility: 2201 - Daniel Den Hoed Hospitaal
city: Bialystok
country: Poland
facility: 1905 - Uniwersytecki Szpital Kliniczny w Białymstoku
city: Gdansk
country: Poland
facility: 1907 - Uniwersyteckie Centrum Kliniczne
city: Kielce
country: Poland
facility: 1908 - Swietokrzyskie Centrum Onkologii
city: Lublin
country: Poland
facility: 1902 - Uniwersytet Medyczny w Lublinie
city: Warsaw
country: Poland
facility: 1901 - Klinika Hematologii - Instytut Hematologii i Transfuzjologii
city: Warsaw
country: Poland
facility: 1906 - MTZ Clinical Research Sp. z o.o.
city: Wrocław
country: Poland
facility: 1904 - Samodzielny Publiczny
city: Bucharest
country: Romania
facility: 2101 - Institutul Clinic Fundeni, Hematologie II
city: Bucharest
country: Romania
facility: 2102 - Spitalul Clinic Coltea, Hematologie
city: Cluj-Napoca
country: Romania
facility: 2106 - Institutul Oncologic "Prof. Dr. I. Chiricuta"
city: Iasi
country: Romania
facility: 2105 - Institutul Regional de Oncologie
city: Moscow
country: Russian Federation
facility: 2001 - Russian Hematology Research Center
city: St. Petersburg
country: Russian Federation
facility: 2003 - Municipal Hospital No. 15
city: Badalona
country: Spain
facility: 1401 - ICO Hospital Germans Trias I Pujol
city: Barcelona
country: Spain
facility: 1404 - Hospital Clínic Servei d´Hematologia
city: La Coruña
country: Spain
facility: 1402 - Complexo Hospitalario Universitario A Coruña
city: Madrid
country: Spain
facility: 1408 - Hospital 12 de Octubre
city: Mallorca
country: Spain
facility: 1405 - Hospital Universitari Son Espases
city: Salamanca
country: Spain
facility: 1407 - Unidad de Citogenética Oncológica
city: Valencia
country: Spain
facility: 1406 - Hospital Universitari i Politècnic La Fe de Valencia
city: Birmingham
country: United Kingdom
facility: 1605 - Queen Elizabeth Hospital
city: Bristol
country: United Kingdom
facility: 1602 - Bristol Royal Infirmary
city: Cardiff
country: United Kingdom
facility: 1604 - University Hospital of Wales
city: London
country: United Kingdom
facility: 1601 - Royal Free Hospital
city: Nottingham
country: United Kingdom
facility: 1607 - Nottingham City Hospital NHS Trust
Study officials:
affiliation: Medizinische Klinik und Poliklinik II, Würzburg
name: Ralf Bargou, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinikum der Goethe Universität Frankfurt
name: Nicola Gökbuget, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gokbuget N, Zugmaier G, Dombret H, Stein A, Bonifacio M, Graux C, Faul C, Bruggemann M, Taylor K, Mergen N, Reichle A, Horst HA, Havelange V, Topp MS, Bargou RC. Curative outcomes following blinatumomab in adults with minimal residual disease B-cell precursor acute lymphoblastic leukemia. Leuk Lymphoma. 2020 Nov;61(11):2665-2673. doi: 10.1080/10428194.2020.1780583. Epub 2020 Jul 3.
citation: Jen EY, Xu Q, Schetter A, Przepiorka D, Shen YL, Roscoe D, Sridhara R, Deisseroth A, Philip R, Farrell AT, Pazdur R. FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease. Clin Cancer Res. 2019 Jan 15;25(2):473-477. doi: 10.1158/1078-0432.CCR-18-2337. Epub 2018 Sep 25.
citation: Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22.
citation: Zhu M, Wu B, Brandl C, Johnson J, Wolf A, Chow A, Doshi S. Blinatumomab, a Bispecific T-cell Engager (BiTE((R))) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications. Clin Pharmacokinet. 2016 Oct;55(10):1271-1288. doi: 10.1007/s40262-016-0405-4.