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

NCT00560794 | Completed Phase 2 Results DMC

• 2 other identifiers: MT103-2022006-006520-19
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to determine whether the bispecific T-cell engager (BiTE®) Blinatumomab (MT103) is effective in the treatment of ALL patients with minimal residual disease.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Minimal Residual Disease; adult ALL; immunotherapeutic treatment; anti-CD19 bispecific antibody derivative; Blinatumomab; MT103

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Minimal Residual Disease (MRD) Response Within 4 Cycles of Treatment

  MRD Response is defined as: * If Philadelphia Chromosome (Ph) positive (+) or translocation (t) (4;11), response was achieved when Ph or t(4;11) was below detection limit and individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4. * If Ph and t(4;11) negative, response was achieved when individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4.

  Within 4 treatment cycles, 24 weeks

Secondary Outcomes (13)

• Percentage of Participants With an MRD Response After Each Treatment Cycle

  At the end of each treatment cycle - Weeks 4, 10, 16, and 22.

• Time to Hematological Relapse

  Up to the data cut-off date of 14 January 2010; maximum duration of follow-up was 564 days.

• Time to MRD Progression

  Up to the data cut-off date of 14 January 2010; Median follow-up time was 155 days

• Time to MRD Relapse

  Up to the data cut-off date of 14 January 2010; Median follow-up time was 116.5 days

• Number of Participants With Adverse Events

  From the start of study treatment until up to 4 weeks after the end of study treatment. The median treatment duration was 87.3 days.

Study Arms (1)

Blinatumomab

EXPERIMENTAL

Participants received blinatumomab as continuous intravenous infusion at constant flow rate over 4 weeks followed by a 2 week treatment-free period (defined as one treatment cycle), for up to a maximum of 10 cycles. The initial dose was 15 μg/m\^2/day. A dose increase to 30 μg/m\^2/day was permitted with evidence for insufficient response to blinatumomab treatment.

Biological: Blinatumomab (MT103)

Interventions

Blinatumomab (MT103) BIOLOGICAL

Administered by continuous intravenous (CIV) over 4 weeks per cycle

Also known as: Blinatumomab, 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:

• B-precursor ALL patients in complete hematological remission with molecular failure or molecular relapse starting at any time after consolidation I of front-line therapy within German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia (GMALL) standards or at any time outside GMALL standards.
• Patients must have a molecular marker for evaluation of minimal residual disease which is either Breakpoint cluster region/gene on human chromosome #9 (Bcr/abl) at any detection level or individual rearrangements of immunoglobulin or T-cell receptor (TCR)-genes measured by an assay with a sensitivity of minimum 10\^-4: At least one individual marker at a quantitative level ≥ 10\^-4.
• Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2
• Ability to understand and willingness to sign a written informed consent
• Signed and dated written informed consent is available

You may not qualify if:

• Current extra medullar involvement
• History of or current relevant central nervous system (CNS) pathology (except migraine/headache and/or previous infiltration of cerebrospinal fluid (CSF) by ALL)
• Current infiltration of cerebrospinal fluid by ALL
• History of or current autoimmune disease
• Autologous stem cell transplantation within 6 weeks prior to study entry
• Any prior allogeneic stem cell transplantation
• Cancer chemotherapy within 4 weeks prior to study treatment (except for intrathecal prophylaxis and/or low dose maintenance therapy such as vinca alkaloids, mercaptopurine, methotrexate, steroids)
• Radiotherapy within 4 weeks prior to study treatment
• Therapy with monoclonal antibodies (Rituximab, MabCampath) within 6 weeks prior to study treatment
• Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
• Presence of human anti-murine antibodies (HAMA)
• Abnormal bone marrow, renal or hepatic function
• Indication for a hypercoagulative state
• History of malignancy other than ALL within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or cervix carcinoma in situ
• Active severe infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator

Sponsors & Collaborators

• Amgen Research (Munich) GmbH: lead

Study Sites (6)

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Julius-Maximilians-Universität Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Klinikum der J.W. Goethe Universität

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, 48129, Germany

Location

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, ´01307, Germany

Location

Universitätsklinikum Schleswig-Holstein im Städtischen Krankenhaus Kiel

Kiel, Schleswig-Holstein, 24116, Germany

Location

Related Publications (3)

• 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

• Zugmaier G, Topp MS, Alekar S, Viardot A, Horst HA, Neumann S, Stelljes M, Bargou RC, Goebeler M, Wessiepe D, Degenhard E, Gokbuget N, Klinger M. Long-term follow-up of serum immunoglobulin levels in blinatumomab-treated patients with minimal residual disease-positive B-precursor acute lymphoblastic leukemia. Blood Cancer J. 2014 Sep 5;4(9):244. doi: 10.1038/bcj.2014.64. No abstract available.

  PMID: 25192414 DERIVED

• Klinger M, Brandl C, Zugmaier G, Hijazi Y, Bargou RC, Topp MS, Gokbuget N, Neumann S, Goebeler M, Viardot A, Stelljes M, Bruggemann M, Hoelzer D, Degenhard E, Nagorsen D, Baeuerle PA, Wolf A, Kufer P. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood. 2012 Jun 28;119(26):6226-33. doi: 10.1182/blood-2012-01-400515. Epub 2012 May 16.

  PMID: 22592608 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Neoplasm, Residual

Interventions

blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• Ralf Bargou, Professor

  Julius-Maximilians-Universität Würzburg

  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: November 19, 2007
• First Posted: November 20, 2007
• Study Start: January 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: November 1, 2014
• Last Updated: January 26, 2015
• Results First Posted: January 7, 2015

Record last verified: 2014-12

Locations

DE (6)