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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT00560794
First received: November 19, 2007
Last updated: November 20, 2012
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Drug: Blinatumomab (MT103)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Multicenter Phase II Study to Investigate the Efficacy, Safety, and Tolerability of the Bispecific T-cell Engager (BiTE®) MT103 in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by Amgen Research (Munich) GmbH:

Primary Outcome Measures:
  • MRD response rate defined by the incidence of MRD negativity [ Time Frame: within 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to hematological relapse [ Time Frame: until hematological relapse ] [ Designated as safety issue: No ]
  • Change in MRD level [ Time Frame: until End of Study (EoS) ] [ Designated as safety issue: No ]
  • Time to molecular relapse [ Time Frame: until molecular relapse ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events [ Time Frame: until EoS ] [ Designated as safety issue: Yes ]
  • Quantification and characterization of peripheral blood lymphocytes [ Time Frame: until EoS ] [ Designated as safety issue: No ]
  • Cytokine serum concentrations [ Time Frame: until EoS ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic parameters [ Time Frame: until EoS ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: October 2007
Estimated Study Completion Date: December 2014
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Patients will receive Blinatumomab (MT103) as continuous intravenous infusion at constant flow rate over 4 weeks followed by a 2 weeks treatment free period, defined as one treatment cycle (up to a maximum of 10 cycles)
Drug: Blinatumomab (MT103)
15µg/m2/24h,30µg/m2/24h, or 60µg/m2/24h continuous intravenous (CIV) over 4 weeks, up to 10 cycles or progression or unacceptable toxicity
Other Names:
  • Blinatumomab
  • AMG103
  • MT103
  • Bispecific anti-CD19 T-cell engager
  • BiTE®

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 =< 1 leukemia cell per 104 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 immu-noglobulins (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-CD19 x anti-CD3 antibody derivative Blinatumomab (MT103).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 GMALL standards or at any time outside GMALL standards.
  • Patients must have a molecular marker for evaluation of minimal residual disease which is either Bcr/abl at any detection level or individual rearrangements of immunoglobulin or TCR-genes measured by an assay with a sensitivity of minimum 10-4: At least one individual marker at a quantitative level ³10-4.
  • 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 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 vincalkaloids, 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 dur-ing participation in the study and at least three months thereafter
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00560794

Locations
Germany
Universitätsklinikum Ulm
Ulm, Baden-Württemberg, Germany, 89081
Julius-Maximilians-Universität Würzburg
Würzburg, Bayern, Germany, 97080
Klinikum der J.W. Goethe Universität
Frankfurt, Hessen, Germany, 60590
Universitätsklinikum Münster
Münster, Nordrhein-Westfalen, Germany, 48129
Universitätsklinikum Carl Gustav Carus
Dresden, Sachsen, Germany, ´01307
Universitätsklinikum Schleswig-Holstein im Städtischen Krankenhaus Kiel
Kiel, Schleswig-Holstein, Germany, 24116
Sponsors and Collaborators
Amgen Research (Munich) GmbH
Investigators
Principal Investigator: Ralf Bargou, Professor Julius-Maximilians-Universität Würzburg
  More Information

No publications provided by Amgen Research (Munich) GmbH

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT00560794     History of Changes
Other Study ID Numbers: MT103-202
Study First Received: November 19, 2007
Last Updated: November 20, 2012
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Amgen Research (Munich) GmbH:
Minimal Residual Disease
adult ALL
immunotherapeutic treatment
anti-CD19 bispecific antibody derivative
Blinatumomab
MT103

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplastic Processes
Pathologic Processes
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 01, 2014