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Safety Study of the Bispecific T-cell Engager Blinatumomab (MT103) in Patients With Relapsed NHL

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT00274742
First received: January 10, 2006
Last updated: January 15, 2015
Last verified: January 2015

January 10, 2006
January 15, 2015
June 2004
August 2011   (final data collection date for primary outcome measure)
Number of Participants With Adverse Events [ Time Frame: From the first infusion of blinatumomab until the safety follow-up visit 2 weeks after end of the treatment period, including the consolidation and relapse periods. The median treatment duration was 33.24 days. ] [ Designated as safety issue: Yes ]
Participants reporting at least one occurence of any adverse event including clinical symptoms, laboratory abnormalities, serious adverse events, and treatment-limiting adverse events
Overall frequency of AEs
Complete list of historical versions of study NCT00274742 on ClinicalTrials.gov Archive Site
  • Serum Concentration of Blinatumomab [ Time Frame: Up to 24 hours after the end of infusion. ] [ Designated as safety issue: No ]
    The steady state serum concentration (Css), summarized as the observed concentrations collected at least 10 hours after the start of continuous intravenous infusion or within the sampling window at the end of infusion. Concentrations below the lower limit of quantitation (100 pg/mL) were excluded from analysis.
  • Objective Tumor Response According to the Cheson Criteria (Without Minimal Response) [ Time Frame: Assessed after 4 and 8 weeks of treatment ] [ Designated as safety issue: No ]

    Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration).

    Best clinical response is defined as the best response achieved during the course of the study, with response defined as: Complete Response, Complete Response Unconfirmed, Partial Response, Stable Disease, and Progressive Disease. In this analysis minimal response is set to stable disease as intended in the response categories according to the Cheson criteria. An independent external review by a radiologist (computed tomography scans) and a pathologist (biopsies) was performed to confirm response status.

    If no post-baseline tumor assessment was available, the overall clinical response was set to not available.

  • Objective Tumor Response According to the Cheson Criteria (With Minimal Response) [ Time Frame: Assessed after 4 and 8 weeks of treatment ] [ Designated as safety issue: No ]

    Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Minimal response was treated as a separate response category in this analysis. Best clinical response was defined as the best response achieved during the course of the study, whereby the following order was applied: Complete Response, Complete Response Unconfirmed, Partial Response, Minimal Response, Stable Disease, and Progressive Disease.

    If no post-baseline tumor assessment was available, the overall clinical response was set to not available.

  • PK and PD measurement
  • Tumour response
Not Provided
Not Provided
 
Safety Study of the Bispecific T-cell Engager Blinatumomab (MT103) in Patients With Relapsed NHL
An Open-label, Multi-center Phase I Study to Investigate the Tolerability and Safety of a Continuous Infusion of the Bispecific T-cell Engager MT103 in Patients With Relapsed Non-Hodgkin's Lymphoma (NHL)

The purpose of this study is to determine whether a continuous infusion of Blinatumomab (MT103) is safe in the treatment of relapsed Non-Hodgkin's Lymphoma.

Furthermore, the study is intended to provide pharmacokinetic and pharmacodynamic data of Blinatumomab as well as to get first indication of tumour activity.

Non-Hodgkin's Lymphoma (NHL) represents the 6th most common cancer. Globally, around 165,000 new cases are diagnosed each year, with approximately 90,000 deaths per year. The vast majority of NHLs are B-cell derived (90%) and express common B-cell antigens such as CD19, CD20 and CD22. NHL can be divided into indolent (low-grade) and aggressive (high-grade) lymphomas. Still almost all patients with advanced stage indolent disease will die from their disease. Therefore, a high medical need exists to develop novel agents that further improve the survival of NHL patients.

Blinatumomab (MT103) is a bispecific antibody derivative, anti-CD19 x anti-CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19+ cells. Data of prior phase I studies show evidence of biological activity in humans. In vitro and ex-vivo data suggest that a longterm presence of the drug in target tissues may provide antitumour activity.

The study investigates the safety and tolerability of different doses of Blinatumomab administration in a continuous infusion regimen. Maximum tolerated dose (MTD) will be defined in a classical 3+3 dose escalation regimen.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-Hodgkin's Lymphoma, Relapsed
Biological: Blinatumomab (MT103)
Doses from 0.5 to 120 µg/m^2/24hours by continuous intravenous infusion
Other Names:
  • Blinatumomab
  • MT103
  • AMG103
  • BLINCYTO™
Experimental: Blinatumomab
Patients received blinatumomab as continuous intravenous infusion for 4 weeks. Participants with clinical benefit were permitted to continue for another 4 weeks for a total of 8 weeks. Participants with a clinical benefit 4 weeks after completion of the first cycle of treatment could also receive additional treatment approximately 3 months ater the end of infusion at the same dose level.
Intervention: Biological: Blinatumomab (MT103)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
76
April 2012
August 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients with first or later relapse of histologically (World Health Organisation classification) confirmed:

    • follicular lymphoma (grade I/II)
    • marginal zone lymphoma
    • lymphoplasmocytic lymphoma
    • mantle cell lymphoma
    • diffuse large B-cell lymphoma
    • small lymphocytic lymphoma requiring therapy and not eligible for curative treatment
  2. Measurable disease (at least one lesion >= 1.5 cm) documented by computed tomography (CT) scan
  3. Age >= 18 years
  4. Eastern Cooperative Oncology Group (ECOG) performance status <=2
  5. Life expectancy of at least 6 months
  6. Ability to understand the patient information and informed consent form
  7. Signed and dated written informed consent is available
  8. B:T cell ratio (Fluorescence-Activated Cell Sorter [FACS] analysis results by central lab) available before study entry.

Exclusion Criteria:

  1. Any other NHL not listed in inclusion criterion 1
  2. Abnormal laboratory values as defined below:

    • Peripheral lymphocyte count > 20 x 10^9/L
    • Platelet counts ≤ 75,000/µL
    • Hemoglobin level ≤ 9 g/dL
    • Venous pH value out of normal range or oxygen saturation ≤ 90%
  3. Known or suspected central nervous system (CNS) involvement by NHL
  4. a)History of or current relevant CNS pathology as epilepsy, seizure, paresis,aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis b)Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI
  5. Autologous stem cell transplantation within 12 weeks prior to study entry
  6. Allogeneic stem cell transplantation
  7. Cancer chemotherapy within 4 weeks prior to study entry
  8. Radiotherapy within 4 weeks prior to study entry
  9. Treatment with rituximab within 4 weeks prior to study entry
  10. Prior treatment with alemtuzumab 12 weeks prior to study entry
  11. Treatment with any investigational agent within 12 weeks prior to study entry
  12. Contraindication for any of the concomitant medications
  13. Abnormal renal or hepatic function as defined below:

    • Aspartate aminotransferase (AST; SGOT) and/or alanine aminotransferase (ALT; SGPT) >= 2 x upper limit of normal (ULN)
    • total bilirubin >= 1.5 x ULN
    • serum creatinine >= 2 x ULN
    • creatinine clearance < 50mL/min
  14. Indication of hypercoagulative state as defined below:

    -antithrombin activity <LLN

  15. Presence of human anti-murine antibodies (HAMA) or known hypersensitivity to immunoglobulins
  16. History of malignancy other than B-cell lymphoma within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix
  17. Active infection / not yet recovered from recent infection; known bacteriemia
  18. Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
  19. Regular dose of corticosteroids during the four weeks prior to D1 of this study or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 4 weeks prior to study entry
  20. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B or hepatitis C virus
  21. Pregnant or nursing women, or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Male patients not willing to ensure that during the study and at least three months thereafter no fathering takes place.
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00274742
MT103-104
Yes
Not Provided
Not Provided
Amgen Research (Munich) GmbH
Amgen Research (Munich) GmbH
Not Provided
Principal Investigator: Ralf Bargou, MD, PhD Medizinische Poliklinik der Julius-Maximilians-Universität Würzburg, Zentrum für Innere Medizin, Oberdürrbacherstr. 6 D-97080 Würzburg
Amgen Research (Munich) GmbH
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP