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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
76
Doses from 0.5 to 120 µg/m\^2/24hours by continuous intravenous infusion
Medizinische Klinik 5, Hämatologie & Internistische Onkologie, Universitätsklinikum Erlangen
Erlangen, Germany
Universitätsklinikum Essen, Klinik für Hämatologie, Medizinische Klinik und Poliklinik
Essen, Germany
Universtätsklinkum Tübingen
Tübingen, Germany
Universitätsklinikum Ulm, Abteilung Innere Medizin III
Ulm, Germany
Number of Participants With Adverse Events
Participants reporting at least one occurence of any adverse event including clinical symptoms, laboratory abnormalities, serious adverse events, and treatment-limiting 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.
Serum Concentration of Blinatumomab
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.
Time frame: Up to 24 hours after the end of infusion.
Objective Tumor Response According to the Cheson Criteria (Without Minimal Response)
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.
Time frame: Assessed after 4 and 8 weeks of treatment
Objective Tumor Response According to the Cheson Criteria (With Minimal Response)
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Medizinische Poliklinik der Julius-Maximilians-Universität Würzburg
Würzburg, Germany
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.
Time frame: Assessed after 4 and 8 weeks of treatment