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

Sponsored by:	Micromet AG
Information provided by:	Micromet AG
ClinicalTrials.gov Identifier:	NCT00560794

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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
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:

MedlinePlus related topics: Animal Bites Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Further study details as provided by Micromet AG:

Primary Outcome Measures:

MRD response rate defined by the incidence of MRD negativity [ Time Frame: within 24 weeks ]

Secondary Outcome Measures:

Time to hematological relapse [ Time Frame: until hematological relapse ]
Change in MRD level [ Time Frame: until End of Study (EoS) ]
Time to molecular relapse [ Time Frame: until molecular relapse ]
Incidence and severity of adverse events [ Time Frame: until EoS ]
Quantification and characterization of peripheral blood lymphocytes [ Time Frame: until EoS ]
Cytokine serum concentrations [ Time Frame: until EoS ]
Pharmacokinetic parameters [ Time Frame: until EoS ]

Estimated Enrollment:	21
Study Start Date:	October 2007
Estimated Study Completion Date:	February 2010

Arms	Assigned Interventions
1: Experimental 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

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

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

Contacts

Contact: Ralf Bargou, Professor	+49 931 202-0 ext 70150	bargou_r@klinik.uni-wuerzburg.de
Contact: Max Topp, MD	+49 931 202-0 ext 70490	topp_m@klinik.uni-wuerzburg.de

Locations

Germany, Baden-Württemberg
Universitätsklinikum Ulm	Recruiting
Ulm, Baden-Württemberg, Germany, 89081
Contact: Andreas Viardot, MD +49 731 500-0 ext 45501 andreas.viardot@uniklinik-ulm.de
Contact: Mathias Schmid, MD +49 731 500-0 ext 45501 mathias.schmid@uniklinik-ulm.de
Principal Investigator: Andreas Viardot, MD
Germany, Bayern
Julius-Maximilians-Universität Würzburg	Recruiting
Würzburg, Bayern, Germany, 97080
Contact: Ralf Bargou, Professor +49 931 201-0 ext 70800 bargou_r@klinik.uni-wuerzburg.de
Contact: Max Topp, MD +49 931 201-0 ext 70490 topp_m@klinik.uni-wuerzburg.de
Principal Investigator: Ralf Bargou, Professor
Germany, Hessen
Klinikum der J.W. Goethe Universität	Recruiting
Frankfurt, Hessen, Germany, 60590
Contact: Nicola Gökbuget, MD +49 69 6301-0 ext 6365 goekbuget@em.uni-frankfurt.de
Contact: Oliver Ottmann, MD +49 69 6301-0 ext 6365 ottmann@em.uni-frankfurt.de
Principal Investigator: Nicola Gökbuget, MD
Germany, Nordrhein-Westfalen
Universitätsklinikum Essen	Recruiting
Essen, Nordrhein-Westfalen, Germany, 45147
Contact: Richard Noppeney, MD +49 201 723-0 ext 3645 richard.noppeney@uk-essen.de
Contact: Christine Kuhnert +49 201 723-0 ext 2553 chrisitine.kuhnert@uk-essen.de
Principal Investigator: Richard Noppeney, MD
Universitätsklinikum Münster	Recruiting
Münster, Nordrhein-Westfalen, Germany, 48129
Contact: Matthias Stelljes, MD +49 251 83-0 ext 52801 stelljes@uni-muenster.de
Contact: Christian Pohlkamp, MD +49 251 83-0 ext 52801 christian.pohlkamp@hotmail.de
Principal Investigator: Matthias Stelljes, MD
Germany, Sachsen
Universitätsklinikum Carl Gustav Carus	Recruiting
Dresden, Sachsen, Germany, ´01307
Contact: Ralph Naumann, MD +49 351 458-0 ext 3855 ralph.naumann@uniklinikum-dresden.de
Contact: Thomas Illmer, MD +49 351 458-0 ext 2046 thomas.illmer@uniklinikum-dresden.de
Principal Investigator: Ralph Naumann, MD
Germany, Schleswig-Holstein
Universitätsklinikum Schleswig-Holstein im Städtischen Krankenhaus Kiel	Recruiting
Kiel, Schleswig-Holstein, Germany, 24116
Contact: Heinz-A. Horst, Professor +49 431 1697-0 ext 1207 h.horst@med2.uni-kiel
Contact: Svenja Neumann, MD +49 431 1697-0 ext 5215
Principal Investigator: Heinz-A. Horst, Professor

Sponsors and Collaborators

Micromet AG

Investigators

Principal Investigator:

Ralf Bargou, Professor

Julius-Maximilians-Universität Würzburg

More Information

No publications provided

Responsible Party:	Micromet AG, Clinical Development ( Gerhard Zugmaier, MD )
Study ID Numbers:	MT103-202
Study First Received:	November 19, 2007
Last Updated:	August 11, 2009
ClinicalTrials.gov Identifier:	NCT00560794 History of Changes
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Micromet AG:

Minimal Residual Disease
adult ALL
immunotherapeutic treatment

anti-CD19 bispecific antibody derivative
Blinatumomab
MT103

Study placed in the following topic categories:

Neoplasm, Residual
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Antibodies, Bispecific
Leukemia
Lymphatic Diseases

Antibodies
Bites and Stings
Lymphoproliferative Disorders
Lymphoma
Acute Lymphoblastic Leukemia
Immunoglobulins

Additional relevant MeSH terms:

Neoplasm, Residual
Lymphatic Diseases
Leukemia
Neoplastic Processes
Neoplasms
Leukemia, Lymphoid

Pathologic Processes
Immunoproliferative Disorders
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on September 11, 2009