Diffuse Large B-cell LymphomaPhase 2NCT01741792
Clinical Study With Blinatumomab in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
A Phase 2 study testing Blinatumomab in people with Diffuse Large B-cell Lymphoma, run by Amgen Research (Munich) GmbH at 6 sites in Germany.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- Blinatumomab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 6 sitesGermany
- Study dates
- Jul 2012to Sep 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Universitätsmedizin
Göttingen
Universitätsklinikum des Saarlandes
Homburg
Universitätsklinikum Schleswig Holstein
Kiel
Klinikum der Johannes-Gutenberg Universität
Mainz
Universitätsklinikum
Ulm
Universititätsklinikum
Würzburg
About this study
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)
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).
Read the 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.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- Blinatumomab
- Keywords
- Relapsed DLBCL, Refractory DLBCL, adult DLBCL, Lymphoma, Non-Hodgkin Lymphoma, Lymphatic diseases, Lymphoproliferative disorders, bispecific antibody, anti-CD19, Immunotherapeutic treatment, Immunoproliferative disorders
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Lymphoma, Non-Hodgkin, Lymphatic Diseases, Lymphoproliferative Disorders, Immunoproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabDrug
Also called AMG103, MT103, BLINCYTO®
Administered by continuous intravenous infusion over 8 weeks in the first cycle and 4 weeks in the second cycle.
| Study group | Role | What they receive |
|---|---|---|
| Blinatumomab | Experimental | 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. Receives: Drug: Blinatumomab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the first 8 weeks
Secondary outcomes (37)
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.
Measured: During the first 8 weeks
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.
Measured: During the first 8 weeks
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.
Measured: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
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.
Measured: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
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.
Measured: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
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.
Measured: From first infusion of blinatumomab until the end of study; median time on follow-up for PFS was 27.0 months.
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.
Measured: From the first infusion of blinatumomab until the end of study; median time on follow-up for overall survival was 26.6 months.
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.
Measured: 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.
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.
Measured: 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)
Leukocyte Counts
Leukocyte (white blood cells) counts were analyzed by differential blood count analysis.
Measured: 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
Lymphocyte Counts
Lymphocyte counts were analyzed by differential blood count analysis.
Measured: 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
Monocyte Counts
Measured: 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
Granulocyte Count
Measured: 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
CD19+ B-Cell Count
CD19+ B-cell counts were analyzed by flow cytometry.
Measured: 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
CD19+ B-Cells as a Percentage of All Lymphocytes
CD19+ B-cell counts were analyzed by flow cytometry.
Measured: 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
CD3+ T-Cell Count
CD3+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD3+ T-Cells as a Percentage of All Lymphocytes
CD3+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD4+ T-Cell Count
CD4+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD4+ T-Cells as a Percentage of All Lymphocytes
CD4+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD8+ T-Cell Count
CD8+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD8+ T-Cells as a Percentage of All Lymphocytes
CD8+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD19+ B-Cell to CD3+ T-Cell Ratio
CD19+ B-cells and CD3+ T-cell counts were analyzed by flow cytometry.
Measured: 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
CD4+ T-Cell to CD8+ T-Cell Ratio
CD4+ T-cells and CD8+ T-cell counts were analyzed by flow cytometry.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2014
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen Research (Munich) GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- - MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01741792
- Sponsor's protocol ID
- MT103-208
- Other IDs
- 2011-005781-38
- Status last verified
- Nov 2016
- First submitted
- 28 Nov 2012
- Last updated
- 6 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27209293Viardot 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.
PubMed 26755709
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01741792
- Acronym / sponsor ID
- MT103-208
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- Relapsed DLBCL, Refractory DLBCL, adult DLBCL, Lymphoma, Non-Hodgkin Lymphoma, Lymphatic diseases, Lymphoproliferative disorders, bispecific antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Amgen Research (Munich) GmbHIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Jul 2014 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 5 Dec 2012 (estimated)
- Results
- Posted 27 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blinatumomab | Experimental | Drug: BlinatumomabBy 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BlinatumomabAlso: AMG103, MT103, BLINCYTO®Administered by continuous intravenous infusion over 8 weeks in the first cycle and 4 weeks in the second cycle. | Drug | Blinatumomab |
Primary outcome
Overall Objective Response Rate During Treatment Cycle 1
Time frame: During the first 8 weeks
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.
37 secondary outcomes
Percentage of Participants With a Best Overall Response of Complete Response
Time frame: During the first 8 weeks
Percentage of Participants With a Best Overall Response of Partial Response
Time frame: During the first 8 weeks
Duration of Objective Response
Time frame: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Duration of Complete Response
Time frame: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Duration of Partial Response
Time frame: From first infusion of blinatumomab until the end of study; median follow-up time for duration of response was 23.7 months.
Progression-free Survival (PFS)
Time frame: From first infusion of blinatumomab until the end of study; median time on follow-up for PFS was 27.0 months.
Overall Survival (OS)
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.
Number of Participants With Adverse Events
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.
Blinatumomab Steady State Serum Concentration
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)
Leukocyte 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
Lymphocyte 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
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
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
CD19+ B-Cell 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
CD19+ B-Cells as a Percentage of All Lymphocytes
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
CD3+ T-Cell 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
CD3+ T-Cells as a Percentage of All Lymphocytes
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
CD4+ T-Cell 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
CD4+ T-Cells as a Percentage of All Lymphocytes
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
CD8+ T-Cell 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
CD8+ T-Cells as a Percentage of All Lymphocytes
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
CD19+ B-Cell to CD3+ T-Cell Ratio
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
CD4+ T-Cell to CD8+ T-Cell Ratio
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
CD4+ Naive T Cell 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
CD4+ Naive T Cells as a Percentage of All CD4+ T-Cells
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
CD4+ Central Memory T-Cell (TCM) 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
CD4+ TCM Cells as a Percentage of All CD4+ T-Cells
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
CD4+ Effector Memory T-Cell (TEM) 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
CD4+ TEM Cells as a Percentage of All CD4+ T-Cells
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
CD8+ Naive T-Cell 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
CD8+ Naive T-Cells as a Percentage of All CD8+ T-Cells
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
CD8+ TCM Cell 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
CD8+ TCM Cells as a Percentage of All CD8+ T-Cells
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
CD8+ Effector Memory T-Cell (TEM) 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
CD8+ TEM Cells as a Percentage of All CD8+ T-Cells
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
CD8+ Terminally Differentiated Effector Memory T-cells (TEMRA) 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
CD8+ TEMRA Cells as a Percentage of All CD8+ T-Cells
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27209293Zhu 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.
- Derived from this study: PubMed 26755709Viardot 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
- MD study director
Amgen
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Blinatumomab in people with Diffuse Large B-cell Lymphoma, run by Amgen Research (Munich) GmbH at 6 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Objective Response Rate During Treatment Cycle 1 (time frame: During the first 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01741792, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2017.