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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier:
NCT01741792
First received: November 28, 2012
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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)


Condition Intervention Phase
Diffuse Large B-cell Lymphoma
Drug: Blinatumomab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Amgen Research (Munich) GmbH:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: within 8 weeks ] [ Designated as safety issue: No ]
    Overall response rate (ORR) within the firt treatment cycle assessed according to Cheson criteria (Cheson et al., 2007)


Secondary Outcome Measures:
  • Complete response (CR) [ Time Frame: within 8 weeks ] [ Designated as safety issue: No ]
    Rate assessed according to Cheson criteria

  • Partial response (PR) [ Time Frame: within 8 weeks ] [ Designated as safety issue: No ]
    Rate assessed according to Cheson criteria

  • Duration of response (by ORR, CR, and PR) [ Time Frame: within 24 months after first treatment cycle ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: within 24 months after first treatment cycle ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: within 24 months after first treatment cycle ] [ Designated as safety issue: No ]
  • Incidence and severity of adverse events [ Time Frame: up to 28 months ] [ Designated as safety issue: Yes ]
  • Blinatumomab serum concentration (pharmacokinetics) [ Time Frame: within 8 weeks ] [ Designated as safety issue: No ]
  • Absolute numbers and proportions of lymphocyte subpopulations [ Time Frame: up to 28 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: July 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Blinatumomab Drug: Blinatumomab
continuous intravenous infusion over 8 weeks in the first cycle and 4 weeks in the second cycle
Other Names:
  • AMG103
  • MT103

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. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01741792

Locations
Germany
Universitätsmedizin
Göttingen, Germany
Universitätsklinikum des Saarlandes
Homburg, Germany
Universitätsklinikum Schleswig Holstein
Kiel, Germany
Klinikum der Johannes-Gutenberg Universität
Mainz, Germany
Universitätsklinikum
Ulm, Germany
Universititätsklinikum
Würzburg, Germany
Sponsors and Collaborators
Amgen Research (Munich) GmbH
Investigators
Study Chair: Andreas Viardot, MD Universitätsklinikum Ulm
  More Information

No publications provided

Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01741792     History of Changes
Other Study ID Numbers: MT103-208, 2011-005781-38
Study First Received: November 28, 2012
Last Updated: April 3, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Amgen Research (Munich) GmbH:
Relapsed DLBCL
Refractory DLBCL
adult DLBCL
Lymphoma
Non-Hodgkin Lymphoma
Lymphatic diseases
Lymphoproliferative disorders
bispecific antibody
anti-CD19
Immunotherapeutic treatment
Immunoproliferative disorders

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014