- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03383978
Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma (CAR2BRAIN)
Multicenter, Open Label, Phase I Study of Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Michael C Burger, PD Dr. med.
- Phone Number: 87711 0049696301
- Email: michael.burger@kgu.de
Study Locations
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-
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Frankfurt, Germany, 60528
- Johann W. Goethe University Hospital, Department of Neurosurgery
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Frankfurt, Germany, 60528
- Johann W. Goethe University Hospital, Senckenberg Institute of Neurooncology
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Baden-Württemberg
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Mannheim, Baden-Württemberg, Germany, 68167
- Neurochirurgische Klinik, Universitätsmedizin Mannheim
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Rheinland-Pfalz
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Mainz, Rheinland-Pfalz, Germany, 55131
- Neurochirurgische Klinik, Universitätsmedizin Mainz
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Recurrent or refractory HER2-positive glioblastoma or its variant gliosarcoma in which relapse surgery (partial or total) or a biopsy (biopsy only for the "CAR2BRAIN-Check" cohort) is being planned. Those patients with planned biopsy may be included into the "CAR2BRAIN-Check" cohort, if all of the following conditions apply:
- Biopsy is necessary (as determined by the treating physician) to rule out the differential diagnosis of pseudoprogression prior to relapse surgery.
- Suspected tumor relapse is located in the wall of an already existing resection cavity.
- This resection cavity has a volume of at least 2.5 ml or is connected to a ventricle or has a broad connection to the surface of the brain.
- Patients must be candidates for relapse surgery, which must be postponable for four weeks.
- Prior therapy must include the standard of care for glioblastoma (radiotherapy and alkylating chemotherapy, or at least a part thereof if the therapy was terminated prematurely due to therapy failure or poor tolerance). For patients with non-methylated MGMT-Promotor, prior alkylating chemotherapy is dispensable.
- Age ≥ 18 years
- Life expectancy ≥ 3 months
- Bilirubin ≤ 3x normal, AST ≤ 5x normal, ALT ≤ 5x normal, serum creatinine ≤ 2x upper limit of normal for age, leukocyte count ≥ 3/nl, thrombocyte count ≥ 100/nl and Hb ≥ 8.0 g/dl
- Blood oxygenation of ≥ 90% as measured by pulse oximetry on room air
- Women must have a negative serum pregnancy test within 72h prior to the start of the first NK-92/5.28.z cell injection.
- Sexually active patients must be willing to utilize effective birth control methods throughout the study and for 24 weeks after the last NK-92/5.28.z cell injection. This includes two different forms of effective contraception (e.g. hormonal contraceptive and condom, IUD/IUS and condom) or sterilization.
- Patients should have been off other antineoplastic therapy for two weeks prior to entry in this study. Temozolomide will be allowed up to 48h preinjection. At the time of inclusion, dexamethasone up to a total dose of 4 mg per day will be allowed if medically indicated.
- Informed consent explained to and signed by patient; patient given copy of informed consent.
- Karnofsky performance score of ≥ 70%
Exclusion criteria:
- Anti-angiogenic therapy e.g. with bevacizumab in the last four weeks prior to study entry
- Previous anti-PD-1 or anti-PD-L1 directed checkpoint inhibitor therapy (only "CAR2BRAIN-Check" cohort)
- Coagulation disorder (INR>1.4 or PTT>50sec) or anticoagulation in therapeutic dosage
- History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. However, patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
- Patients with Type I diabetes mellitus not on a stable dose of insulin regimen
Psoriatic arthritis (however, patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are permitted provided that they meet all of the following conditions:
- Rash must cover less than 10% of body surface area
- Disease is well controlled at baseline and only requiring low potency topical steroids
- No acute exacerbations of underlying condition within the previous 12 months (not requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids))
- Patients with clinical or laboratory signs for immunodeficiency or under immunosuppressive medication other than corticosteroids
- Severe intercurrent infection
- Known HIV, HBV (defined by detection of HBsAg) or HCV positivity (defined by detection of HCV-IgG)
- Chronic heart failure NYHA ≥III
- Patients with a prior solid organ transplantation or allogenic haematopoietic stem cell transplantation
- Patients unable to undergo MRI
- Pregnancy or breastfeeding
- Drug or alcohol abuse
- Severe psychiatric disorder which might interfere with the study treatment or examination
- Simultaneous participation in another interventional clinical trial. If a subject participated in a trial testing another IMP, such IMP should have been terminated at least 30 days before inclusion of the subject.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: NK-92/5.28.z + Ezabenlimab
Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8; intravenous infusion of Ezabenlimab 240mg q 3 weeks
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Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8
Intravenous infusion of Ezabenlimab 240mg q 3 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Time Frame: 24 weeks
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24 weeks
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Maximum tolerated dose (MTD) or maximum feasible dose (MFD) for NK-92/5.28.z
Time Frame: 24 weeks
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24 weeks
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Period of detectability of NK-92/5.28.z cells in blood and cerebrospinal fluid (CSF) during the first 24 weeks after NK-92/5.28.z application with qPCR.
Time Frame: 24 weeks
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qPCR detection of NK-92/5.28.z in blood or CSF
|
24 weeks
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Cytokine profile in the blood and the cerebrospinal fluid.
Time Frame: 24 weeks
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
NK-92- and/or CAR 5.28.z-directed immune response.
Time Frame: 24 weeks
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24 weeks
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Objective response rate.
Time Frame: 24 weeks
|
24 weeks
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Progression-free survival.
Time Frame: 24 weeks
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24 weeks
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Overall survival.
Time Frame: 24 weeks
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24 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Michael C Burger, PD Dr. med., Johann W. Goethe University Hospital, Frankfurt am Main, Germany
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- EudraCT 2016-000225-39
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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