Status:
ACTIVE_NOT_RECRUITING
Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma
Lead Sponsor:
Johann Wolfgang Goethe University Hospital
Collaborating Sponsors:
DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH
Georg-Speyer-Haus
Conditions:
Glioblastoma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
The main objective of this clinical study is to evaluate the safety and tolerability of NK-92/5.28.z and to determine the maximum tolerated dose or maximum feasible dose (MFD). Recommended phase 2 dos...
Eligibility Criteria
Inclusion
- 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.
Exclusion
Key Trial Info
Start Date :
December 1 2017
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
June 30 2026
Estimated Enrollment :
42 Patients enrolled
Trial Details
Trial ID
NCT03383978
Start Date
December 1 2017
End Date
June 30 2026
Last Update
March 27 2024
Active Locations (4)
Enter a location and click search to find clinical trials sorted by distance.
1
Neurochirurgische Klinik, Universitätsmedizin Mannheim
Mannheim, Baden-Wurttemberg, Germany, 68167
2
Neurochirurgische Klinik, Universitätsmedizin Mainz
Mainz, Rhineland-Palatinate, Germany, 55131
3
Johann W. Goethe University Hospital, Department of Neurosurgery
Frankfurt, Germany, 60528
4
Johann W. Goethe University Hospital, Senckenberg Institute of Neurooncology
Frankfurt, Germany, 60528