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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03383978
Recruitment Status : Recruiting
First Posted : December 27, 2017
Last Update Posted : May 16, 2019
Sponsor:
Collaborators:
DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH
Georg-Speyer-Haus
LOEWE Center for Cell and Gene Therapy
Information provided by (Responsible Party):
Michael Burger, Johann Wolfgang Goethe University Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Glioblastoma Biological: NK-92/5.28.z Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter, Open Label, Phase I Study of Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: NK-92/5.28.z
Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8
 Biological: NK-92/5.28.z
Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03. [ Time Frame: 24 weeks ]
  2. Maximum tolerated dose (MTD) or maximum feasible dose (MFD). [ Time Frame: 24 weeks ]
  3. 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

  4. Cytokine profile in the blood and the cerebrospinal fluid. [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. NK-92- and/or CAR 5.28.z-directed immune response. [ Time Frame: 24 weeks ]
  2. Objective response rate. [ Time Frame: 24 weeks ]
  3. Progression-free survival. [ Time Frame: 24 weeks ]
  4. Overall survival. [ Time Frame: 24 weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03383978


Contacts
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Contact: Michael C Burger, Dr. med. 0049696301 ext 87711 michael.burger@kgu.de

Locations
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Germany
Johann W. Goethe University Hospital, Department of Neurosurgery Recruiting
Frankfurt, Germany, 60528
Contact: Christian Senft, Prof. Dr. med.    0049696301 ext 5295    christian.senft@kgu.de   
Johann W. Goethe University Hospital, Senckenberg Institute of Neurooncology Recruiting
Frankfurt, Germany, 60528
Contact: Michael C Burger, Dr. med.    0049696301 ext 87711    michael.burger@kgu.de   
Contact: Joachim P Steinbach, Prof. Dr. med.    0049696301 ext 87711    joachim.steinbach@med.uni-frankfurt.de   
Sponsors and Collaborators
Johann Wolfgang Goethe University Hospital
DRK Blutspendedienst Baden-Württemberg-Hessen gGmbH
Georg-Speyer-Haus
LOEWE Center for Cell and Gene Therapy
Investigators
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Principal Investigator: Michael C Burger, Dr. med. Johann W. Goethe University Hospital, Frankfurt am Main, Germany
More Information
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Responsible Party: Michael Burger, Principal Investigator, Johann Wolfgang Goethe University Hospital
ClinicalTrials.gov Identifier: NCT03383978    
Other Study ID Numbers: EudraCT 2016-000225-39
First Posted: December 27, 2017    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
 Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue