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

NCT ID: NCT01207388

Last Updated: 2020-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2019-01-07

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.

Conditions

B-cell Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

Continuous intravenous infusion

Interventions

Blinatumomab

Continuous intravenous infusion

Intervention Type: DRUG

Other Intervention Names

AMG 103; MT103; BLINCYTO™

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen Research (Munich) GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralf Bargou, MD

Role: PRINCIPAL_INVESTIGATOR

Medizinische Klinik und Poliklinik II, Würzburg

Nicola Gökbuget, MD

Role: PRINCIPAL_INVESTIGATOR

Klinikum der Goethe Universität Frankfurt

Locations

1102 - LKH Graz

Graz, , Austria

1107 - Krankenhaus der Elisabethinen

Linz, , Austria

1106

Salzburg, , Austria

1101 - AKH Wien

Vienna, , Austria

1504

Antwerp, , Belgium

1505

Bruges, , Belgium

1502 - Cliniques Universitaires de Saint-Luc

Brussels, , Belgium

1503

Ghent, , 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

Hanover, , 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

Wroclaw, , 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

Iași, , Romania

2001 - Russian Hematology Research Center

Moscow, , Russia

2003 - Municipal Hospital No. 15

Saint Petersburg, , Russia

1402 - Complexo Hospitalario Universitario A Coruña

A Coruña, , Spain

1401 - ICO Hospital Germans Trias I Pujol

Badalona, , Spain

1404 - Hospital Clínic Servei d´Hematologia

Barcelona, , 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

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

Countries

Austria; Belgium; France; Germany; Italy; Netherlands; Poland; Romania; Russia; Spain; United Kingdom

References

Chevallier P. Should patients with Ph-negative acute lymphoblastic leukaemia who reach minimal residual disease negativity have HSCT? Lancet Haematol. 2024 Jan;11(1):e12-e13. doi: 10.1016/S2352-3026(23)00365-4. No abstract available.

Reference Type: DERIVED

PMID: 38135369 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32619115 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30254079 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29358182 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27209293 (View on PubMed)

Other Identifiers

MT103-203

Identifier Type: -

Identifier Source: org_study_id