Title

Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
Multicenter, Open Label, Phase I Study of Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
  • Phase

    Phase 1
  • Study Type

    Interventional
  • Status

    Recruiting
  • Study Participants

    30
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.
Study Started
Dec 01
2017
Primary Completion
Sep 30
2022
Anticipated
Study Completion
Dec 31
2022
Anticipated
Last Update
Sep 25
2020

Biological NK-92/5.28.z

Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8

NK-92/5.28.z Experimental

Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8

Criteria

Inclusion Criteria:

Recurrent or refractory HER2-positive glioblastoma or its variant gliosarcoma in which a relapse surgery (partial or total) or a biopsy (patients with a biopsy are only eligible for the escalation cohort) is being planned. In patients with a planned biopsy, a maximum diameter of the contrast-enhancing lesion from which the biopsy will be done of 3 cm measured in the most recent magnetic resonance imaging at the time of enrollment to the study is allowed.
Prior therapy must include the standard of care for glioblastoma (radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide according to the EORTC 26981 trial or at least a part thereof if the standard therapy was terminated prematurely due to therapy failure or poor tolerance).
Age ≥ 18 years.
Life expectancy ≥ 3 months.
Bilirubin ≤ 3x normal, AST ≤ 5x normal, ALT ≤ 5x, 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 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 ≥ 50%.

Exclusion Criteria:

Anti-angiogenic therapy e.g. with bevacizumab (Avastin®) in the last four weeks prior to study entry.
Coagulation disorder (INR>1.4 or PTT>50sec) or anticoagulation at therapeutic dosage.
Active autoimmune disease.
Patients with clinical or laboratory signs for immunodeficiency or under immunosuppressive medication other than corticosteroids.
Severe intercurrent infection.
Known HIV, HBV or HCV positivity.
Chronic heart failure NYHA ≥III.
Patients with a prior solid organ transplantation or allogenic haematopoietic stem cell transplantation.
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 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.
No Results Posted