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Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma (CAR2BRAIN)

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ClinicalTrials.gov Identifier: NCT03383978
Recruitment Status : Recruiting
First Posted : December 27, 2017
Last Update Posted : September 25, 2020
Sponsor:
Collaborators:
DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH
Georg-Speyer-Haus
LOEWE Center Frankfurt Cancer Institute
German Cancer Research Center
Information provided by (Responsible Party):
Michael Burger, Johann Wolfgang Goethe University Hospital

Tracking Information
First Submitted Date  ICMJE November 30, 2017
First Posted Date  ICMJE December 27, 2017
Last Update Posted Date September 25, 2020
Actual Study Start Date  ICMJE December 1, 2017
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2017)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: 24 weeks ]
  • Maximum tolerated dose (MTD) or maximum feasible dose (MFD). [ Time Frame: 24 weeks ]
  • 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 ]
    qPCR detection of NK-92/5.28.z in blood or CSF
  • Cytokine profile in the blood and the cerebrospinal fluid. [ Time Frame: 24 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2017)
  • NK-92- and/or CAR 5.28.z-directed immune response. [ Time Frame: 24 weeks ]
  • Objective response rate. [ Time Frame: 24 weeks ]
  • Progression-free survival. [ Time Frame: 24 weeks ]
  • Overall survival. [ Time Frame: 24 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
Official Title  ICMJE Multicenter, Open Label, Phase I Study of Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glioblastoma
Intervention  ICMJE Biological: NK-92/5.28.z
Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8
Study Arms  ICMJE Experimental: NK-92/5.28.z
Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8
Intervention: Biological: NK-92/5.28.z
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 19, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date September 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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.
  2. 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).
  3. Age ≥ 18 years.
  4. Life expectancy ≥ 3 months.
  5. 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.
  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 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 ≥ 50%.

Exclusion Criteria:

  1. Anti-angiogenic therapy e.g. with bevacizumab (Avastin®) in the last four weeks prior to study entry.
  2. Coagulation disorder (INR>1.4 or PTT>50sec) or anticoagulation at therapeutic dosage.
  3. Active autoimmune disease.
  4. Patients with clinical or laboratory signs for immunodeficiency or under immunosuppressive medication other than corticosteroids.
  5. Severe intercurrent infection.
  6. Known HIV, HBV or HCV positivity.
  7. Chronic heart failure NYHA ≥III.
  8. Patients with a prior solid organ transplantation or allogenic haematopoietic stem cell transplantation.
  9. Unable to undergo MRI.
  10. Pregnancy or breastfeeding.
  11. Drug or alcohol abuse.
  12. Severe psychiatric disorder which might interfere with the study treatment or examination.
  13. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael C Burger, PD Dr. med. 0049696301 ext 87711 michael.burger@kgu.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03383978
Other Study ID Numbers  ICMJE EudraCT 2016-000225-39
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael Burger, Johann Wolfgang Goethe University Hospital
Study Sponsor  ICMJE Johann Wolfgang Goethe University Hospital
Collaborators  ICMJE
  • DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH
  • Georg-Speyer-Haus
  • LOEWE Center Frankfurt Cancer Institute
  • German Cancer Research Center
Investigators  ICMJE
Principal Investigator: Michael C Burger, PD Dr. med. Johann W. Goethe University Hospital, Frankfurt am Main, Germany
PRS Account Johann Wolfgang Goethe University Hospital
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP