Non-Hodgkin's Lymphoma, RelapsedPhase 1NCT00274742
Safety Study of the Bispecific T-cell Engager Blinatumomab (MT103) in Patients With Relapsed NHL
A Phase 1 study testing Blinatumomab (MT103) in people with Non-Hodgkin's Lymphoma, Relapsed, run by Amgen Research (Munich) GmbH at 5 sites in Germany.
Trial summary
The purpose of this study is to determine whether a continuous infusion of Blinatumomab (MT103) is safe in the treatment of relapsed Non-Hodgkin's Lymphoma. Furthermore, the study is intended to provide pharmacokinetic and pharmacodynamic data of Blinatumomab as well as to get first indication of tumour activity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Relapsed
- What is being tested?
- Blinatumomab (MT103)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 5 sitesGermany
- Study dates
- Jun 2004to Apr 2012
- Phase
- Phase 1
- 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 first or later relapse of histologically (World Health Organisation classification) confirmed:
- follicular lymphoma (grade I/II)
- marginal zone lymphoma
- lymphoplasmocytic lymphoma
- mantle cell lymphoma
- diffuse large B-cell lymphoma
Show all 14Show fewer
- small lymphocytic lymphoma requiring therapy and not eligible for curative treatment
- Measurable disease (at least one lesion >= 1.5 cm) documented by computed tomography (CT) scan
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status <=2
- Life expectancy of at least 6 months
- Ability to understand the patient information and informed consent form
- Signed and dated written informed consent is available
- B:T cell ratio (Fluorescence-Activated Cell Sorter [FACS] analysis results by central lab) available before study entry.
Who cannot join
- Any other NHL not listed in inclusion criterion 1
- Abnormal laboratory values as defined below:
- Peripheral lymphocyte count > 20 x 10^9/L
- Platelet counts ≤ 75,000/µL
- Hemoglobin level ≤ 9 g/dL
- Venous pH value out of normal range or oxygen saturation ≤ 90%
Show all 30Show fewer
- Known or suspected central nervous system (CNS) involvement by NHL
- a)History of or current relevant CNS pathology as epilepsy, seizure, paresis,aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis b)Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI
- Autologous stem cell transplantation within 12 weeks prior to study entry
- Allogeneic stem cell transplantation
- Cancer chemotherapy within 4 weeks prior to study entry
- Radiotherapy within 4 weeks prior to study entry
- Treatment with rituximab within 4 weeks prior to study entry
- Prior treatment with alemtuzumab 12 weeks prior to study entry
- Treatment with any investigational agent within 12 weeks prior to study entry
- Contraindication for any of the concomitant medications
- Abnormal renal or hepatic function as defined below:
- Aspartate aminotransferase (AST; SGOT) and/or alanine aminotransferase (ALT; SGPT) >= 2 x upper limit of normal (ULN)
- total bilirubin >= 1.5 x ULN
- serum creatinine >= 2 x ULN
- creatinine clearance < 50mL/min
- Indication of hypercoagulative state as defined below:
- -antithrombin activity <LLN
- Presence of human anti-murine antibodies (HAMA) or known hypersensitivity to immunoglobulins
- History of malignancy other than B-cell lymphoma within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or carcinoma in situ of the cervix
- Active infection / not yet recovered from recent infection; known bacteriemia
- Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
- Regular dose of corticosteroids during the four weeks prior to D1 of this study or anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or any other immunosuppressive therapy within 4 weeks prior to study entry
- Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B or hepatitis C virus
- Pregnant or nursing women, or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Male patients not willing to ensure that during the study and at least three months thereafter no fathering takes place.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Medizinische Klinik 5, Hämatologie & Internistische Onkologie, Universitätsklinikum Erlangen
Erlangen, 91054
Universitätsklinikum Essen, Klinik für Hämatologie, Medizinische Klinik und Poliklinik
Essen, 45147
Universtätsklinkum Tübingen
Tübingen, 72076
Universitätsklinikum Ulm, Abteilung Innere Medizin III
Ulm, 89081
Medizinische Poliklinik der Julius-Maximilians-Universität Würzburg
Würzburg, 97080
About this study
Official title: An Open-label, Multi-center Phase I Study to Investigate the Tolerability and Safety of a Continuous Infusion of the Bispecific T-cell Engager MT103 in Patients With Relapsed Non-Hodgkin's Lymphoma (NHL)
The purpose of this study is to determine whether a continuous infusion of Blinatumomab (MT103) is safe in the treatment of relapsed Non-Hodgkin's Lymphoma.
Furthermore, the study is intended to provide pharmacokinetic and pharmacodynamic data of Blinatumomab as well as to get first indication of tumour activity.
Read the detailed description
Non-Hodgkin's Lymphoma (NHL) represents the 6th most common cancer. Globally, around 165,000 new cases are diagnosed each year, with approximately 90,000 deaths per year. The vast majority of NHLs are B-cell derived (90%) and express common B-cell antigens such as CD19, CD20 and CD22. NHL can be divided into indolent (low-grade) and aggressive (high-grade) lymphomas. Still almost all patients with advanced stage indolent disease will die from their disease. Therefore, a high medical need exists to develop novel agents that further improve the survival of NHL patients.
Blinatumomab (MT103) is a bispecific antibody derivative, anti-CD19 x anti-CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19+ cells. Data of prior phase I studies show evidence of biological activity in humans. In vitro and ex-vivo data suggest that a longterm presence of the drug in target tissues may provide antitumour activity.
The study investigates the safety and tolerability of different doses of Blinatumomab administration in a continuous infusion regimen. Maximum tolerated dose (MTD) will be defined in a classical 3+3 dose escalation regimen.
- Conditions
- Non-Hodgkin's Lymphoma, Relapsed
- Being tested
- Blinatumomab (MT103)
- Keywords
- Non-Hodgkin's Lymphoma, Cancer immunotherapy, Monoclonal antibody, anti-CD19, anti-CD3, BiTE, Blinatumomab
- Medical subject headings
- Lymphoma, Non-Hodgkin, Recurrence, Bites and Stings
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blinatumomab (MT103)Biological
Also called Blinatumomab, MT103, AMG103, BLINCYTO™
Doses from 0.5 to 120 µg/m^2/24hours by continuous intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Blinatumomab | Experimental | Patients received blinatumomab as continuous intravenous infusion for 4 weeks. Participants with clinical benefit were permitted to continue for another 4 weeks for a total of 8 weeks. Participants with a clinical benefit 4 weeks after completion of the first cycle of treatment could also receive additional treatment approximately 3 months ater the end of infusion at the same dose level. Receives: Biological: Blinatumomab (MT103) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events
Participants reporting at least one occurence of any adverse event including clinical symptoms, laboratory abnormalities, serious adverse events, and treatment-limiting adverse events
Measured: From the first infusion of blinatumomab until the safety follow-up visit 2 weeks after end of the treatment period, including the consolidation and relapse periods. The median treatment duration was 33.24 days.
Secondary outcomes (3)
Serum Concentration of Blinatumomab
The steady state serum concentration (Css), summarized as the observed concentrations collected at least 10 hours after the start of continuous intravenous infusion or within the sampling window at the end of infusion. Concentrations below the lower limit of quantitation (100 pg/mL) were excluded from analysis.
Measured: Up to 24 hours after the end of infusion.
Objective Tumor Response According to the Cheson Criteria (Without Minimal Response)
Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration).
Best clinical response is defined as the best response achieved during the course of the study, with response defined as: Complete Response, Complete Response Unconfirmed, Partial Response, Stable Disease, and Progressive Disease. In this analysis minimal response is set to stable disease as intended in the response categories according to the Cheson criteria. An independent external review by a radiologist (computed tomography scans) and a pathologist (biopsies) was performed to confirm response status.
If no post-baseline tumor assessment was available, the overall clinical response was set to not available.
Measured: Assessed after 4 and 8 weeks of treatment
Objective Tumor Response According to the Cheson Criteria (With Minimal Response)
Tumor response was defined according to the Cheson criteria and assessed after 4 and 8 weeks of study treatment using computed tomography (CT) scan (neck, thorax and abdomen/pelvic to assess nodal disease/organ enlargement due to nodal/diffuse infiltration), and bone marrow biopsy (to assess bone marrow infiltration). Minimal response was treated as a separate response category in this analysis. Best clinical response was defined as the best response achieved during the course of the study, whereby the following order was applied: Complete Response, Complete Response Unconfirmed, Partial Response, Minimal Response, Stable Disease, and Progressive Disease.
If no post-baseline tumor assessment was available, the overall clinical response was set to not available.
Measured: Assessed after 4 and 8 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2006 (estimated)
- Study startJun 2004
- Primary completionAug 2011
- Study completionApr 2012
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 Non-Hodgkin's Lymphoma, RelapsedStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen Research (Munich) GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ralf Bargou, MD, PhD, Principal investigator, Medizinische Poliklinik der Julius-Maximilians-Universität Würzburg, Zentrum für Innere Medizin, Oberdürrbacherstr. 6 D-97080 Würzburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00274742
- Sponsor's protocol ID
- MT103-104
- Status last verified
- Jan 2015
- First submitted
- 10 Jan 2006
- Last updated
- 16 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Nagele V, Zugmaier G, Goebeler ME, Viardot A, Bargou R, Kufer P, Klinger M. Relationship of T- and B-cell kinetics to clinical response in patients with relapsed/refractory non-Hodgkin lymphoma treated with blinatumomab. Exp Hematol. 2021 Aug;100:32-36. doi: 10.1016/j.exphem.2021.06.005. Epub 2021 Jul 3.
PubMed 34228983Zhu 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 27209293
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center Phase I Study to Investigate the Tolerability and Safety of a Continuous Infusion of the Bispecific T-cell Engager MT103 in Patients With Relapsed Non-Hodgkin's Lymphoma (NHL)
- ClinicalTrials.gov ID
- NCT00274742
- Acronym / sponsor ID
- MT103-104
- Conditions
- Non-Hodgkin's Lymphoma, Relapsed
- Keywords
- Non-Hodgkin's Lymphoma, Cancer immunotherapy, Monoclonal antibody, anti-CD19, anti-CD3, BiTE, Blinatumomab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Amgen Research (Munich) GmbHIndustry (pharma, biotech, devices)
- Study start
- Jun 2004
- Primary completion
- Aug 2011 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 11 Jan 2006 (estimated)
- Results
- Posted 16 Jan 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 determine whether a continuous infusion of Blinatumomab (MT103) is safe in the treatment of relapsed Non-Hodgkin's Lymphoma.
Furthermore, the study is intended to provide pharmacokinetic and pharmacodynamic data of Blinatumomab as well as to get first indication of tumour activity.
Detailed description
Non-Hodgkin's Lymphoma (NHL) represents the 6th most common cancer. Globally, around 165,000 new cases are diagnosed each year, with approximately 90,000 deaths per year. The vast majority of NHLs are B-cell derived (90%) and express common B-cell antigens such as CD19, CD20 and CD22. NHL can be divided into indolent (low-grade) and aggressive (high-grade) lymphomas. Still almost all patients with advanced stage indolent disease will die from their disease. Therefore, a high medical need exists to develop novel agents that further improve the survival of NHL patients.
Blinatumomab (MT103) is a bispecific antibody derivative, anti-CD19 x anti-CD3, designed to link B-cells and T-cells resulting in T-cell activation and a cytotoxic T-cell response against CD19+ cells. Data of prior phase I studies show evidence of biological activity in humans. In vitro and ex-vivo data suggest that a longterm presence of the drug in target tissues may provide antitumour activity.
The study investigates the safety and tolerability of different doses of Blinatumomab administration in a continuous infusion regimen. Maximum tolerated dose (MTD) will be defined in a classical 3+3 dose escalation regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blinatumomab | Experimental | Biological: Blinatumomab (MT103)Patients received blinatumomab as continuous intravenous infusion for 4 weeks. Participants with clinical benefit were permitted to continue for another 4 weeks for a total of 8 weeks. Participants with a clinical benefit 4 weeks after completion of the first cycle of treatment could also receive additional treatment approximately 3 months ater the end of infusion at the same dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with first or later relapse of histologically (World Health Organisation classification) confirmed:
- Measurable disease (at least one lesion >= 1.5 cm) documented by computed tomography (CT) scan
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status <=2
- Life expectancy of at least 6 months
Key exclusion criteria (30 listed)
- Any other NHL not listed in inclusion criterion 1
- Abnormal laboratory values as defined below:
- Known or suspected central nervous system (CNS) involvement by NHL
- a)History of or current relevant CNS pathology as epilepsy, seizure, paresis,aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis b)Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI
- Autologous stem cell transplantation within 12 weeks prior to study entry
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 |
|---|---|---|
| Blinatumomab (MT103)Also: Blinatumomab, MT103, AMG103, BLINCYTO™Doses from 0.5 to 120 µg/m^2/24hours by continuous intravenous infusion | Biological | Blinatumomab |
Primary outcome
Number of Participants With Adverse Events
Time frame: From the first infusion of blinatumomab until the safety follow-up visit 2 weeks after end of the treatment period, including the consolidation and relapse periods. The median treatment duration was 33.24 days.
Participants reporting at least one occurence of any adverse event including clinical symptoms, laboratory abnormalities, serious adverse events, and treatment-limiting adverse events
3 secondary outcomes
Serum Concentration of Blinatumomab
Time frame: Up to 24 hours after the end of infusion.
Objective Tumor Response According to the Cheson Criteria (Without Minimal Response)
Time frame: Assessed after 4 and 8 weeks of treatment
Objective Tumor Response According to the Cheson Criteria (With Minimal Response)
Time frame: Assessed after 4 and 8 weeks of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34228983Nagele V, Zugmaier G, Goebeler ME, Viardot A, Bargou R, Kufer P, Klinger M. Relationship of T- and B-cell kinetics to clinical response in patients with relapsed/refractory non-Hodgkin lymphoma treated with blinatumomab. Exp Hematol. 2021 Aug;100:32-36. doi: 10.1016/j.exphem.2021.06.005. Epub 2021 Jul 3.
- 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.
Related trials for Non-Hodgkin's Lymphoma, Relapsed
RecruitingPhase 1/2
Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed/Refractory B-cell Lymphoma
Lymphoma, Non-Hodgkin Lymphoma
Active, not recruitingPhase 1
A Study of Radiation Therapy Before CAR T Cell Therapy for People With B Cell Lymphoma
Non-Hodgkin Lymphoma, Non-Hodgkin's Lymphoma, Relapsed
RecruitingPhase 1/2
A Study to Evaluate Glofitamab Monotherapy and Glofitamab + Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma
Mature B-Cell Non-Hodgkin Lymphoma
RecruitingPhase 1
In VIVO CAR-T Therapy for Relapsed/Refractory Hematological Malignancies
B-Acute Lymphoblastic Leukemia, B Cell Non-Hodgkin's Lymphoma
RecruitingPhase 3
A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy
Large B-cell Lymphoma, Lymphoma, B-Cell
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.
Ralf Bargou, MD, PhD principal investigator
Medizinische Poliklinik der Julius-Maximilians-Universität Würzburg, Zentrum für Innere Medizin, Oberdürrbacherstr. 6 D-97080 Würzburg
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Blinatumomab (MT103) in people with Non-Hodgkin's Lymphoma, Relapsed, run by Amgen Research (Munich) GmbH at 5 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 14 inclusion and 30 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 16 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 16 Jan 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?
Number of Participants With Adverse Events (time frame: From the first infusion of blinatumomab until the safety follow-up visit 2 weeks after end of the treatment period, including the consolidation and relapse periods. The median treatment duration was 33.24 days.). 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 NCT00274742, 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 16 Jan 2015.