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Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Primary Purpose

Diffuse Large B-cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Blinatumomab
Sponsored by
Amgen Research (Munich) GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring Relapsed DLBCL, Refractory DLBCL, adult DLBCL, Lymphoma, Non-Hodgkin Lymphoma, Lymphatic diseases, Lymphoproliferative disorders, bispecific antibody, anti-CD19, Immunotherapeutic treatment, Immunoproliferative disorders

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with Diffuse Large B-Cell Lymphoma (DLBCL) who are refractory to first or later treatment or have a first relapse or later relapse not eligible for autologous hematopoietic stem cell transplant (HSCT) or relapsed post- autologous-HSCT
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Age ≥ 18 years
  • Life expectancy of ≥ 12 weeks
  • Cerebrospinal fluid (CSF) free of infiltration by DLBCL

Exclusion Criteria:

  • History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis
  • Current infiltration of CSF by DLBCL
  • History of autoimmune disease with potential CNS involvement or current autoimmune disease
  • Autologous HSCT within six weeks prior to start of blinatumomab treatment
  • Prior allogeneic HSCT
  • Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
  • Radiotherapy within four weeks prior to start of blinatumomab treatment
  • Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treatment
  • Any investigational anti-lymphoma product within four weeks prior to start of blinatumomab treatment
  • Treatment with any other investigational product after signature of informed consent
  • Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
  • Abnormal laboratory values indicative of inadequate renal or liver function
  • History of malignancy other than non-Hodgkin's lymphoma (NHL) within five years prior to start of blinatumomab treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
  • Active uncontrolled infection, any other concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
  • Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus
  • Pregnant or nursing women
  • Previous treatment with blinatumomab
  • Presence of human anti-murine antibodies (HAMA) at screening

Sites / Locations

  • Universitätsmedizin
  • Universitätsklinikum des Saarlandes
  • Universitätsklinikum Schleswig Holstein
  • Klinikum der Johannes-Gutenberg Universität
  • Universitätsklinikum
  • Universititätsklinikum

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Blinatumomab

Arm Description

By study design, two dose regimens were assessed in this study. In Stage 1, Cohort 1, participants received blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during cycle 1. In Cohort 2, the next participants enrolled and received a constant dose of 112 µg/day blinatumomab. The dosing regimen with the more favorable benefit-risk profile was then selected for Stage 2, Cohort 3.

Outcomes

Primary Outcome Measures

Overall Objective Response Rate During Treatment Cycle 1
Overall response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all evidence of disease and partial response is defined as regression of measureable disease and no new sites.

Secondary Outcome Measures

Percentage of Participants With a Best Overall Response of Complete Response
Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Complete response is defined as the disappearance of all evidence of disease.
Percentage of Participants With a Best Overall Response of Partial Response
Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (<50% decrease in size of masses) of measureable disease and no new sites.
Duration of Objective Response
The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Duration of Complete Response
The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Duration of Partial Response
The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Progression-free Survival (PFS)
The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment.
Overall Survival (OS)
The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed.
Number of Participants With Adverse Events
Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. An adverse event or suspected adverse drug reaction was considered "serious" if it resulted in one of the following outcomes: Resulted in death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions; Was a congenital anomaly or birth defect; Was a medically important condition. The Investigator used medical judgment to determine whether there was a causal relationship (ie, related [reasonably possible] or unrelated [not reasonably possible]) between an adverse event and blinatumomab.
Blinatumomab Steady State Serum Concentration
Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day.
Leukocyte Counts
Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.
Lymphocyte Counts
Lymphocyte counts were analyzed by differential blood count analysis.
Monocyte Counts
Granulocyte Count
CD19+ B-Cell Count
CD19+ B-cell counts were analyzed by flow cytometry.
CD19+ B-Cells as a Percentage of All Lymphocytes
CD19+ B-cell counts were analyzed by flow cytometry.
CD3+ T-Cell Count
CD3+ T-cell counts were analyzed by flow cytometry.
CD3+ T-Cells as a Percentage of All Lymphocytes
CD3+ T-cell counts were analyzed by flow cytometry.
CD4+ T-Cell Count
CD4+ T-cell counts were analyzed by flow cytometry.
CD4+ T-Cells as a Percentage of All Lymphocytes
CD4+ T-cell counts were analyzed by flow cytometry.
CD8+ T-Cell Count
CD8+ T-cell counts were analyzed by flow cytometry.
CD8+ T-Cells as a Percentage of All Lymphocytes
CD8+ T-cell counts were analyzed by flow cytometry.
CD19+ B-Cell to CD3+ T-Cell Ratio
CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.
CD4+ T-Cell to CD8+ T-Cell Ratio
CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.
CD4+ Naive T Cell Count
CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells
CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD4+ Central Memory T-Cell (TCM) Count
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
CD4+ TCM Cells as a Percentage of All CD4+ T-Cells
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
CD4+ Effector Memory T-Cell (TEM) Count
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD4+ TEM Cells as a Percentage of All CD4+ T-Cells
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD8+ Naive T-Cell Count
CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells
CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD8+ TCM Cell Counts
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
CD8+ TCM Cells as a Percentage of All CD8+ T-Cells
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
CD8+ Effector Memory T-Cell (TEM) Count
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD8+ TEM Cells as a Percentage of All CD8+ T-Cells
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count
Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.
CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells
Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.

Full Information

First Posted
November 28, 2012
Last Updated
November 9, 2016
Sponsor
Amgen Research (Munich) GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT01741792
Brief Title
Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Official Title
An Open Label, Multicenter, Exploratory Phase 2 Study to Evaluate the Efficacy and Safety of the Bispecific T-Cell Engager (BiTE®) Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen Research (Munich) GmbH

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to confirm whether the bispecific T-cell engager blinatumomab is effective and safe in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Detailed Description
DLBCL is an aggressive malignant disease which evolves from B-cells and affects mainly the lymphatic tissue. Due to its aggressive nature the disease is characterized by a fast course which is lethal without therapy. Potentially curative therapy options are available even at advanced stages. Standard-first line leads to a high initial response rate (85-90%) and an approximate cure rate of 50% of patients. Patients refractory to or with early relapse after this treatment (10-15%) have a very poor prognosis. Blinatumomab is a bispecific single-chain antibody derivative against CD19 and CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19 expressing cells. This study consisted of a screening period, treatment period, and a follow-up efficacy and survival period. The core study comprises the treatment period to the 30 days after the last infusion. The first cycle consisted of a continuous intravenous (CIV) infusion over 8 weeks. Participants who achieved a Complete Response (CR) or Partial Response (PR) or had stable disease after the first treatment cycle were eligible to receive a second (consolidation) cycle of treatment over 4 weeks, following a 4-week treatment-free interval. After the last treatment cycle, efficacy and survival follow-up visits occurred for up to 24 months from treatment start. Participants who relapsed during the follow-up period may have received an additional 8 weeks of treatment. Two dose regimens were assessed in this study. Stage 1 comprised 2 dose cohorts. In Cohort 1, the first 6 participants were to receive blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during Cycle 1. In Cohort 2, the next 6 participants enrolled were to receive a constant dose of 112 µg/day blinatumomab. Before the initiation of stage 2, a pre-planned data monitoring committee (DMC) meeting was held to assess the safety profile of Cohort 1 and Cohort 2. The dosing regimen with the more favorable benefit-risk profile was to be selected for Cohort 3.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
Relapsed DLBCL, Refractory DLBCL, adult DLBCL, Lymphoma, Non-Hodgkin Lymphoma, Lymphatic diseases, Lymphoproliferative disorders, bispecific antibody, anti-CD19, Immunotherapeutic treatment, Immunoproliferative disorders

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blinatumomab
Arm Type
Experimental
Arm Description
By study design, two dose regimens were assessed in this study. In Stage 1, Cohort 1, participants received blinatumomab in a dose-escalating manner: 9 µg/day for the first week, followed by 28 µg/day for the second week, then 112 µg/day for the remaining 6 weeks of treatment during cycle 1. In Cohort 2, the next participants enrolled and received a constant dose of 112 µg/day blinatumomab. The dosing regimen with the more favorable benefit-risk profile was then selected for Stage 2, Cohort 3.
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Other Intervention Name(s)
AMG103, MT103, BLINCYTO®
Intervention Description
Administered by continuous intravenous infusion over 8 weeks in the first cycle and 4 weeks in the second cycle.
Primary Outcome Measure Information:
Title
Overall Objective Response Rate During Treatment Cycle 1
Description
Overall response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Overall objective response rate (ORR) is the percentage of participants with a best overall response of complete response (CR) or partial response (PR). Complete response is defined as the disappearance of all evidence of disease and partial response is defined as regression of measureable disease and no new sites.
Time Frame
During the first 8 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Best Overall Response of Complete Response
Description
Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Complete response is defined as the disappearance of all evidence of disease.
Time Frame
During the first 8 weeks
Title
Percentage of Participants With a Best Overall Response of Partial Response
Description
Response within the first treatment cycle was assessed according to Cheson criteria by a central reader. Response was evaluated using computerized tomography (CT) scans and positron emission tomography (PET) (to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Partial response is defined as regression (<50% decrease in size of masses) of measureable disease and no new sites.
Time Frame
During the first 8 weeks
Title
Duration of Objective Response
Description
The time from documentation of the first assessment of either partial or complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time Frame
From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Title
Duration of Complete Response
Description
The time from documentation of the first assessment of complete response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time Frame
From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Title
Duration of Partial Response
Description
The time from documentation of the first assessment of partial response until the start of new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death, whichever is the earliest event. A patient who did not have new anti-tumor treatment (excluding any stem cell transplantation), progression of disease, or death was censored at last tumor assessment date. Disease progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time Frame
From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Title
Progression-free Survival (PFS)
Description
The time from the date of first blinatumomab infusion until the date of diagnosis of progression of lymphoma, the start date of new anti-tumor treatment (excluding any stem cell transplantation) or date of death, whichever is the earliest. Patients alive who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were censored at last date of tumor assessment.
Time Frame
From first infusion of blinatumomab until the end of study; median time on follow-up for PFS was 27.0 months.
Title
Overall Survival (OS)
Description
The time from the date of first blinatumomab infusion until death as a result of any cause. Patients still alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. For patients who withdrew their informed consent, only information until the date of withdrawal was analyzed.
Time Frame
From the first infusion of blinatumomab until the end of study; median time on follow-up for overall survival was 26.6 months.
Title
Number of Participants With Adverse Events
Description
Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. An adverse event or suspected adverse drug reaction was considered "serious" if it resulted in one of the following outcomes: Resulted in death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant incapacity or substantial disruption to conduct normal life functions; Was a congenital anomaly or birth defect; Was a medically important condition. The Investigator used medical judgment to determine whether there was a causal relationship (ie, related [reasonably possible] or unrelated [not reasonably possible]) between an adverse event and blinatumomab.
Time Frame
From the first dose of blinatumomab until up to 30 days after the last dose or until the data cut-off date of 10 July 2014, whichever occurred first; the overall median duration of treatment exposure was 46.8 days.
Title
Blinatumomab Steady State Serum Concentration
Description
Blinatumomab serum levels were analyzed using a validated cluster of differentiation (CD)69 activation bioassay with a lower limit of quantification (LLOQ) of 50 pg/mL. Steady-state concentration (Css) was based on actual dose received, rather than based on cohort or time or day.
Time Frame
Cycle 1: predose; Day 3 and Day 8 (Css for 9 ug/day); Day 15 (Css for 28 ug/day); and Day 29, Day 43 and Day 57 (Css for 112 ug/day)
Title
Leukocyte Counts
Description
Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
Lymphocyte Counts
Description
Lymphocyte counts were analyzed by differential blood count analysis.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
Monocyte Counts
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
Granulocyte Count
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD19+ B-Cell Count
Description
CD19+ B-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD19+ B-Cells as a Percentage of All Lymphocytes
Description
CD19+ B-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD3+ T-Cell Count
Description
CD3+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD3+ T-Cells as a Percentage of All Lymphocytes
Description
CD3+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ T-Cell Count
Description
CD4+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ T-Cells as a Percentage of All Lymphocytes
Description
CD4+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ T-Cell Count
Description
CD8+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ T-Cells as a Percentage of All Lymphocytes
Description
CD8+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD19+ B-Cell to CD3+ T-Cell Ratio
Description
CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ T-Cell to CD8+ T-Cell Ratio
Description
CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ Naive T Cell Count
Description
CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells
Description
CD4+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ Central Memory T-Cell (TCM) Count
Description
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ TCM Cells as a Percentage of All CD4+ T-Cells
Description
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ Effector Memory T-Cell (TEM) Count
Description
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD4+ TEM Cells as a Percentage of All CD4+ T-Cells
Description
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ Naive T-Cell Count
Description
CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells
Description
CD8+ naive T-cell counts are native T-cells characterized by the cell-surface expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ TCM Cell Counts
Description
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ TCM Cells as a Percentage of All CD8+ T-Cells
Description
Central memory T cells are characterized by the cell-surface expression of CD197 but not CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ Effector Memory T-Cell (TEM) Count
Description
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ TEM Cells as a Percentage of All CD8+ T-Cells
Description
Effector memory T cells are characterized by the lack of expression of CD197 and CD45RA and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) Count
Description
Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment
Title
CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells
Description
Terminally differentiated effector memory T cells are characterized by the cell-surface expression of CD45RA but not CD197 and were analyzed by flow cytometry.
Time Frame
Screening (Day -20 to Day 0), Day 1 pre-infusion, Days 8, 15, 29, 43, end of infusion (day 53), end of core study (day 87), and follow-up at 3, 6, 9, 12, 15, 18, 21 and 24 months after the first response assessment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with Diffuse Large B-Cell Lymphoma (DLBCL) who are refractory to first or later treatment or have a first relapse or later relapse not eligible for autologous hematopoietic stem cell transplant (HSCT) or relapsed post- autologous-HSCT Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Age ≥ 18 years Life expectancy of ≥ 12 weeks Cerebrospinal fluid (CSF) free of infiltration by DLBCL Exclusion Criteria: History or presence of clinically relevant central nervous system (CNS) pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis Current infiltration of CSF by DLBCL History of autoimmune disease with potential CNS involvement or current autoimmune disease Autologous HSCT within six weeks prior to start of blinatumomab treatment Prior allogeneic HSCT Cancer chemotherapy within two weeks prior to start of blinatumomab treatment Radiotherapy within four weeks prior to start of blinatumomab treatment Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treatment Any investigational anti-lymphoma product within four weeks prior to start of blinatumomab treatment Treatment with any other investigational product after signature of informed consent Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation Abnormal laboratory values indicative of inadequate renal or liver function History of malignancy other than non-Hodgkin's lymphoma (NHL) within five years prior to start of blinatumomab treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix Active uncontrolled infection, any other concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus Pregnant or nursing women Previous treatment with blinatumomab Presence of human anti-murine antibodies (HAMA) at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
- MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Universitätsmedizin
City
Göttingen
Country
Germany
Facility Name
Universitätsklinikum des Saarlandes
City
Homburg
Country
Germany
Facility Name
Universitätsklinikum Schleswig Holstein
City
Kiel
Country
Germany
Facility Name
Klinikum der Johannes-Gutenberg Universität
City
Mainz
Country
Germany
Facility Name
Universitätsklinikum
City
Ulm
Country
Germany
Facility Name
Universititätsklinikum
City
Würzburg
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
27209293
Citation
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.
Results Reference
derived
PubMed Identifier
26755709
Citation
Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. doi: 10.1182/blood-2015-06-651380. Epub 2016 Jan 11.
Results Reference
derived

Learn more about this trial

Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

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