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

NCT01207388 | Completed Phase 2 Results DMC

• 1 other identifier: MT103-203
• Study Type: interventional
• Target: 116
• Locations: 11 countries
• Sites: 75

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.

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Minimal Residual Disease (MRD) Response Within the First Treatment Cycle

  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 Outcomes (11)

• Hematological Relapse-free Survival (RFS)

  18 months, up to the data cut-off date of 05 August 2015

• Overall Survival

  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

  100 days after HSCT, as of the data cut-off date of 05 August 2015

• Time to Hematological Relapse

  Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.

• Duration of Complete MRD Response

  Until the data cut-off date of 05 August 2015; median time on study was 18.3 months.

Study Arms (1)

Blinatumomab

EXPERIMENTAL

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

Interventions

Blinatumomab DRUG

Continuous intravenous infusion

Also known as: AMG 103, MT103, BLINCYTO™

Blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen Research (Munich) GmbH: lead

Study Sites (75)

1102 - LKH Graz

Graz, Austria

Location

1107 - Krankenhaus der Elisabethinen

Linz, Austria

Location

1106

Salzburg, Austria

Location

1101 - AKH Wien

Vienna, Austria

Location

1504

Antwerp, Belgium

Location

1505

Bruges, Belgium

Location

1502 - Cliniques Universitaires de Saint-Luc

Brussels, Belgium

Location

1503

Ghent, Belgium

Location

1501 - Cliniques Universitaires UCL de Mont Godinne

Yvoir, Belgium

Location

1211 - CHU d'Angers

Angers, France

Location

1210 - CHU de Besançon

Besançon, France

Location

1206 - Hôpital de Pontoise

Cergy-Pontoise, France

Location

1205 - CHU Henri Mondor

Créteil, France

Location

1209 - CHU de Lyon

Lyon, France

Location

1212 - Hôpital de l'hôtel Dieu

Nantes, France

Location

1213 - Centre Hospitalier Universitaire de Nice

Nice, France

Location

1201 - Hôpital Saint Louis

Paris, France

Location

1202 - CHU de Bordeaux - Hôpital Haut Lévêque

Pessac, France

Location

1208 - CHU de Purpan

Toulouse, France

Location

1011 - Charité Berlin

Berlin, Germany

Location

1022 - Universitätsklinkum Carl Gustav Carus Dresden

Dresden, Germany

Location

1009 - Universitätsklinikum Essen

Essen, Germany

Location

1002 - Klinikum der Goethe Universität

Frankfurt, Germany

Location

1014 - Asklepiosklinik St. Georg

Hamburg, Germany

Location

1018 - Medizinische Hochschule Hannover

Hanover, Germany

Location

1012 - Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

1003 - Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

1019 - Universitätsklinikum Leipzig

Leipzig, Germany

Location

1010 - Klinikum der Universität München - Großhadern

Munich, Germany

Location

1004 - Universitätsklinikum Münster

Münster, Germany

Location

1016 - Universitätsklinikum Regensburg

Regensburg, Germany

Location

1020 - Universitätsklinikum Rostock

Rostock, Germany

Location

1007 - Robert-Bosch-Krankenhaus

Stuttgart, Germany

Location

1015 - Universitätsklinikum Tübingen

Tübingen, Germany

Location

1005 - Universitätsklinikum Ulm

Ulm, Germany

Location

1001 - Julius-Maximilians-Universität Würzburg

Würzburg, Germany

Location

1301 - Ospedali Riuniti di Bergamo

Bergamo, Italy

Location

1303 - Istituto di Ematologia "L.& A.Seràgnoli" Azienda

Bologna, Italy

Location

1314 - Azienda Ospedaliera Spedali Civili Brescia

Brescia, Italy

Location

1313 - Universita di Catania

Catania, Italy

Location

1312 - Azienda Ospedaliera Universitaria San Martino

Genoa, Italy

Location

1305 - Ospedale San Gerardo

Monza, Italy

Location

1309 - Azienda Ospedaliera Antonio Cardarelli

Napoli, Italy

Location

1308 - Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, Italy

Location

1302 - Università La Sapienza di Roma

Rome, Italy

Location

1310 - Fondazione Policlinico Tor Vergata

Rome, Italy

Location

1315 - Azienda Ospedaliero-Universitaria S. Giovanni Battista (Le Molinette)

Torino, Italy

Location

1311 - Azienda Ospedaliera di Verona

Verona, Italy

Location

2204 - UMC Groningen

Groningen, Netherlands

Location

2201 - Daniel Den Hoed Hospitaal

Rotterdam, Netherlands

Location

1905 - Uniwersytecki Szpital Kliniczny w Białymstoku

Bialystok, Poland

Location

1907 - Uniwersyteckie Centrum Kliniczne

Gdansk, Poland

Location

1908 - Swietokrzyskie Centrum Onkologii

Kielce, Poland

Location

1902 - Uniwersytet Medyczny w Lublinie

Lublin, Poland

Location

1901 - Klinika Hematologii - Instytut Hematologii i Transfuzjologii

Warsaw, Poland

Location

1906 - MTZ Clinical Research Sp. z o.o.

Warsaw, Poland

Location

1904 - Samodzielny Publiczny

Wroclaw, Poland

Location

2101 - Institutul Clinic Fundeni, Hematologie II

Bucharest, Romania

Location

2102 - Spitalul Clinic Coltea, Hematologie

Bucharest, Romania

Location

2106 - Institutul Oncologic "Prof. Dr. I. Chiricuta"

Cluj-Napoca, Romania

Location

2105 - Institutul Regional de Oncologie

Iași, Romania

Location

2001 - Russian Hematology Research Center

Moscow, Russia

Location

2003 - Municipal Hospital No. 15

Saint Petersburg, Russia

Location

1402 - Complexo Hospitalario Universitario A Coruña

A Coruña, Spain

Location

1401 - ICO Hospital Germans Trias I Pujol

Badalona, Spain

Location

1404 - Hospital Clínic Servei d´Hematologia

Barcelona, Spain

Location

1408 - Hospital 12 de Octubre

Madrid, Spain

Location

1405 - Hospital Universitari Son Espases

Mallorca, Spain

Location

1407 - Unidad de Citogenética Oncológica

Salamanca, Spain

Location

1406 - Hospital Universitari i Politècnic La Fe de Valencia

Valencia, Spain

Location

1605 - Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

1602 - Bristol Royal Infirmary

Bristol, United Kingdom

Location

1604 - University Hospital of Wales

Cardiff, United Kingdom

Location

1601 - Royal Free Hospital

London, United Kingdom

Location

1607 - Nottingham City Hospital NHS Trust

Nottingham, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 38135369 DERIVED

• 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.

  PMID: 32619115 DERIVED

• 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.

  PMID: 30254079 DERIVED

• 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.

  PMID: 29358182 DERIVED

• 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.

  PMID: 27209293 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Neoplasm, Residual; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Lymphatic Diseases; Lymphoproliferative Disorders

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Hematologic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• Ralf Bargou, MD

  Medizinische Klinik und Poliklinik II, Würzburg

  PRINCIPAL INVESTIGATOR

• Nicola Gökbuget, MD

  Klinikum der Goethe Universität Frankfurt

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2010
• First Posted: September 22, 2010
• Study Start: November 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: January 7, 2019
• Last Updated: February 10, 2020
• Results First Posted: February 12, 2015

Record last verified: 2020-01

Locations

FR (10); GB (5); BE (5); RU (2); ES (7); PL (7); DE (17); NL (2); IT (12); RO (4); AU (4)