Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

NCT01466179 | Completed Phase 2 Results DMC

• 2 other identifiers: MT103-2112011-002257-61
• Study Type: interventional
• Target: 225
• Locations: 6 countries
• Sites: 39

Brief Summary

The purpose of this study is to confirm whether the bispecific T cell engager antibody blinatumomab (MT103) is effective and safe in the treatment of patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL).

Conditions

Acute Lymphoblastic Leukemia

Keywords

B-ALL; relapsed ALL; refractory ALL; adult ALL; Leukemia; Leukemia, Lymphoid; precursor cell lymphoblastic leukemia-lymphoma; Lymphatic diseases; Lymphoproliferative disorders; bispecific antibody; anti-CD19; Immunotherapeutic treatment; immunoproliferative disorders

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

  Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: Complete Remission (CR): * bone marrow blasts ≤ 5% * no evidence of disease * full recovery of peripheral blood counts: * platelets \> 100,000/μL, and * absolute neutrophil count (ANC) \> 1,000/μL Complete Remission With Partial Hematological Recovery (CRh\*): * bone marrow blasts ≤ 5% * no evidence of disease * partial recovery of peripheral blood counts: * platelets \> 50,000/μL, and * ANC \> 500/μL.

  Within the first 2 cycles of treatment, 12 weeks

Secondary Outcomes (14)

• Time to Hematological Relapse (Duration of Response)

  Up to the data cut-off date of 10 October 2013; median observation time was 8.0 months.

• Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission

  Up to the data cut-off date of 10 October 2013. Maximum duration on study was 17.8 months.

• Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

• Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

• Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

Study Arms (1)

Blinatumomab

EXPERIMENTAL

Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first seven days of treatment, escalated to 28 μg/day starting from Week 2 of treatment.

Biological: Blinatumomab

Interventions

Blinatumomab BIOLOGICAL

Continuous intravenous infusion over four weeks per treatment cycle

Also known as: AMG103, 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 Philadelphia chromosome (Ph)-negative B-precursor ALL, with any of the following:
• relapsed or refractory with first remission duration less than or equal to 12 months in first salvage or
• relapsed or refractory after first salvage therapy or
• relapsed or refractory within 12 months of allogeneic hematopoietic stem cell transplantation (HSCT)
• % or more blasts in bone marrow
• In case of clinical signs of additional extramedullary disease: measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Age ≥ 18 years

You may not qualify if:

• Patients with Ph-positive ALL
• Patients with Burkitt's Leukemia according to World Health organization (WHO) classification
• History or presence of clinically relevant central nervous system (CNS) pathology
• Active ALL in the CNS or testes
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement
• Autologous HSCT within six weeks prior to start of blinatumomab treatment
• Allogeneic HSCT within three months prior to start of blinatumomab treatment
• Any active acute graft versus-host disease (GvHD), or active chronic GvHD Grade 2 - 4
• Any systemic therapy against GvHD within two weeks prior to start of blinatumomab treatment
• Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
• Radiotherapy within two weeks prior to start of blinatumomab treatment
• Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treat-ment
• Any investigational anti-leukemic product within four weeks prior to start of blinatumomab treatment
• Treatment with any other investigational medicinal product (IMP) after signature of informed consent
• Eligibility for allogeneic HSCT at the time of enrollment

Sponsors & Collaborators

• Amgen Research (Munich) GmbH: lead

Study Sites (39)

City of Hope

Duarte, California, 91010-3000, United States

Location

University of California Los Angeles

Los Angeles, California, 90095-1678, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Institute

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Streets

Buffalo, New York, 14263, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

CHU d'Angers

Angers, 49933, France

Location

Hôpital de l'hôtel Dieu

Nantes, 44000, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

CHU de Purpan

Toulouse, 31059, France

Location

Charité - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

Klinikum der Goethe Universität, Medizinische Klinik II

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24116, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Julius-Maximilians-Universität, Medizinische Klinik und Poliklinik II

Würzburg, 97080, Germany

Location

Ospedali Riuniti di Bergamo

Bergamo, 24128, Italy

Location

Azienda Ospedaliera Antonio Cardarelli

Naples, 80131, Italy

Location

Ospedali Riuniti "Villa Sofia-Cervello"

Palermo, 90146, Italy

Location

Università La Sapienza di Roma

Rome, 00161, Italy

Location

Azienda Ospedaliero-Universitaria

Turin, 10126, Italy

Location

Azienda Ospedaliera di Verona

Verona, 37134, Italy

Location

ICO Hospital Germans Trias I Pujol

Badalona, 08916, Spain

Location

Hospital Clínic Servei d´Hematologia

Barcelona, 08036, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

University Hospitals Bristol NHS

Bristol, BS2 8ED, United Kingdom

Location

Royal Free Hampstead NHS Trust

London, NW3 2QG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (6)

• Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

  PMID: 35622074 DERIVED

• Gokbuget N, Kantarjian HM, Bruggemann M, Stein AS, Bargou RC, Dombret H, Fielding AK, Heffner L, Rigal-Huguet F, Litzow M, O'Brien S, Zugmaier G, Gao S, Nagorsen D, Forman SJ, Topp MS. Molecular response with blinatumomab in relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Blood Adv. 2019 Oct 22;3(20):3033-3037. doi: 10.1182/bloodadvances.2019000457.

  PMID: 31648325 DERIVED

• Zhu M, Kratzer A, Johnson J, Holland C, Brandl C, Singh I, Wolf A, Doshi S. Blinatumomab Pharmacodynamics and Exposure-Response Relationships in Relapsed/Refractory Acute Lymphoblastic Leukemia. J Clin Pharmacol. 2018 Feb;58(2):168-179. doi: 10.1002/jcph.1006. Epub 2017 Sep 18.

  PMID: 28922466 DERIVED

• Barlev A, Lin VW, Katz A, Hu K, Cong Z, Barber B. Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data. Adv Ther. 2017 Jan;34(1):148-155. doi: 10.1007/s12325-016-0447-x. Epub 2016 Nov 21.

  PMID: 27873237 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

• Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16.

  PMID: 25524800 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Leukemia, Lymphoid; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• Nicola Gökbuget, MD

  Klinikum der Goethe Universität Frankfurt

  PRINCIPAL INVESTIGATOR

• Max Topp, MD

  Julius-Maximilians-Universität, Medizinische Klinik und Poliklinik II, Würzburg

  PRINCIPAL INVESTIGATOR

• Hagop Kantarjian, MD

  MD Anderson Cancer Center, Houston, Texas

  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: October 28, 2011
• First Posted: November 7, 2011
• Study Start: December 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2017
• Last Updated: August 18, 2017
• Results First Posted: January 22, 2015

Record last verified: 2017-07

Locations

ES (5); US (12); GB (3); IT (6); DE (9); FR (4)