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)
18 Years
N/A
Both
Diffuse Large B-cell Lymphoma
Trial Information
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)
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. In vitro data indicate CD19+ lymphoma and leukemia cell lines
to be extremely sensitive to blinatumomab-mediated cytotoxicity. A phase 1 study (MT103-104)
has indicated dose-dependent efficacy and acceptable tolerability of blinatumomab in
patients with relapsed B-cell Non-Hodgkin's Lymphoma (B-NHL).
The purpose of this study is to confirm wether the bispecific T-cell engager blinatumomab is
effective and safe in the treatment of patients with relapsed/refractory Diffuse Large
B-cell Lymphoma (DLBCL). The patients will be treated with 2 different dosing schedules of
continuous intravenous blinatumomab treatment .
Patients will receive up to 2 cycles (first cycle 8 weeks, second cycle 4 weeks.
Inclusion Criteria:
Sample size: 25 evaluable patients
Study population 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 auto- HSCT
or relapsed post- autologous-HSCT
- 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 CNS pathology as epilepsy, seizure,
paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease,
cerebellar disease, organic brain syndrome, psychosis
- Current infiltration of cerebro-spinal fluid (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 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 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Overall response rate (ORR)
Outcome Description:
Overall response rate (ORR) within the firt treatment cycle assessed according to Cheson criteria (Cheson et al., 2007)
Outcome Time Frame:
within 8 weeks
Safety Issue:
No
Principal Investigator
Andreas Viardot, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Universitätsklinikum Ulm
Authority:
Germany: Paul-Ehrlich-Institut
Study ID:
MT103-208
NCT ID:
NCT01741792
Start Date:
July 2012
Completion Date:
January 2014
Related Keywords:
- Diffuse Large B-Cell Lymphoma
- Relapsed DLBCL
- Refractory DLBCL
- adult DLBCL
- Lymphoma
- Non-Hodgkin Lymphoma
- Lymphatic diseases
- Lymphoproliferative disorders
- bispecific antibody
- anti-CD19
- Immunotherapeutic treatment
- Immunoproliferative disorders
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
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