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

NCT ID: NCT00560794

Last Updated: 2015-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2014-11-30

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.

Detailed Description

The presence of leukemia cells below the cytological detection limit (5% leukemic cells) is defined as minimal residual disease (MRD). If no MRD is detectable (< 10^-4 = less than 1 leukemia cell per 10^4 bone marrow cells) a complete molecular remission is reached. In the last years a series of retrospective studies has shown that MRD in adult ALL is an independent prognostic factor as already demonstrated for childhood leukemia. Diagnostic tools for MRD are polymerase chain reaction (PCR) and/or flow cytometry. PCR analysis can detect fusion transcripts such as bcr/abl and individual clonal rearrangements of immunoglobulins (IgH) and/or T-cell receptor genes (TCR). About 25% of patients with MRD defined by rearrangement comprise a high-risk group with a 94% relapse rate within 3 years. In general for patients with MRD, who are not eligible for allogenic stem cell transplantation, curative treatment is not available. This accounts for MRD defined by the Philadelphia chromosome translocation as well as for MRD defined by rearrangement. The current study is set up to address the question of treating MRD positive ALL with the bispecific anti-cluster of differentiation (CD)19 x anti-CD3 antibody derivative blinatumomab (MT103).

Conditions

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 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.

Group Type: EXPERIMENTAL

Blinatumomab (MT103)

Intervention Type: BIOLOGICAL

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

Interventions

Blinatumomab (MT103)

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Blinatumomab; AMG103; MT103; BLINCYTO™

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive)
• Pregnant or nursing women
• Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter

• 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, Professor

Role: PRINCIPAL_INVESTIGATOR

Julius-Maximilians-Universität Würzburg

Locations

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Julius-Maximilians-Universität Würzburg

Würzburg, Bavaria, Germany

Klinikum der J.W. Goethe Universität

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, Germany

Universitätsklinikum Carl Gustav Carus

Dresden, Saxony, Germany

Universitätsklinikum Schleswig-Holstein im Städtischen Krankenhaus Kiel

Kiel, Schleswig-Holstein, Germany

Countries

Germany

References

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)

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.

Reference Type: DERIVED

PMID: 25192414 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22592608 (View on PubMed)

Other Identifiers

2006-006520-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MT103-202

Identifier Type: -

Identifier Source: org_study_id