NCT03383978 Intracranial Injection of NK-92/5.28.z Cells in Combination With Intravenous Ezabenlimab in Patients With Recurrent HER2-positive Glioblastoma
| NCT ID | NCT03383978 |
| Status | Recruiting |
| Phase | Phase 1 |
| Sponsor | Johann Wolfgang Goethe University Hospital |
| Condition | Glioblastoma |
| Study Type | INTERVENTIONAL |
| Enrollment | 42 participants |
| Start Date | 2017-12-01 |
| Primary Completion | 2027-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 42 participants in total. It began in 2017-12-01 with a primary completion date of 2027-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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 doses both for intraoperative injections only (RP2Diio) and repetitive injections (RP2Dri) will be determined. Frequent side effects and target organs of toxicity and their severity, duration and reversibility will be determined. Furthermore, pharmacokinetics and pharmacodynamics will be examined. In addition, potential signs of anti-tumor activity of NK-92/5.28.z cells will be analyzed. In the separate "CAR2BRAIN-Check" and "CAR2BRAIN-CheckR" cohorts, combination therapy of NK-92/5.28.z with the anti-PD-1 antibody Ezabenlimab (BI 754091) will be tested.
Eligibility Criteria
Inclusion Criteria: 1. 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-CheckR" cohort) is being planned. Those patients with planned biopsy may be included into the "CAR2BRAIN-CheckR" 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. * Patients must be candidates for relapse surgery, which must be postponable for four weeks. 2. 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. 3. Age ≥ 18 years 4. Life expectancy ≥ 3 months 5. 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 6. Blood oxygenation of ≥ 90% as measured by pulse oximetry on room air 7. Women must have a negative serum pregnancy test within 72h prior to the start of the first NK-92/5.28.z cell injection. 8. 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. 9. 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. 10. Informed consent explained to and signed by patient; patient given copy of informed consent. 11. Karnofsky performance score of ≥ 70% Exclusion criteria: 1. Anti-angiogenic therapy e.g. with bevacizumab in the last four weeks prior to study entry 2. Previous anti-PD-1 or anti-PD-L1 directed checkpoint inhibitor therapy (only "CAR2BRAIN-Check" cohort) 3. Coagulation disorder (INR\>1.4 or PTT\>50sec) or anticoagulation in therapeutic dosage 4. 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. 5. Patients with Type I diabetes mellitus not on a stable dose of insulin regimen 6. 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)) 7. Patients with clinical or laboratory signs for immunodeficiency or under immunosuppressive medication other than corticosteroids 8. Severe intercurrent infection 9. Known HIV, HBV (defined by detection of HBsAg) or HCV positivity (defined by detection of HCV-IgG) 10. Chronic heart failure NYHA ≥III 11. Patients with a prior solid organ transplantation or allogenic haematopoietic stem cell transplantation 12. Patients unable to undergo MRI 13. Pregnancy or breastfeeding 14. Drug or alcohol abuse 15. Severe psychiatric disorder which might interfere with the study treatment or examination 16. 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.
Contact & Investigator
Michael C Burger, PD Dr. med.
PRINCIPAL INVESTIGATOR
Johann W. Goethe University Hospital, Frankfurt am Main, Germany
Frequently Asked Questions
Who can join the NCT03383978 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Glioblastoma. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT03383978 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT03383978 currently recruiting?
Yes, NCT03383978 is actively recruiting participants. Contact the research team at michael.burger@unimedizin-ffm.de for enrollment information.
Where is the NCT03383978 trial being conducted?
This trial is being conducted at Heidelberg, Germany, Mannheim, Germany, Mainz, Germany, Frankfurt, Germany and 1 additional location.
Who is sponsoring the NCT03383978 clinical trial?
NCT03383978 is sponsored by Johann Wolfgang Goethe University Hospital. The principal investigator is Michael C Burger, PD Dr. med. at Johann W. Goethe University Hospital, Frankfurt am Main, Germany. The trial plans to enroll 42 participants.
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