Trial document




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  DRKS00013333

Trial Description

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Title

Single center, open label, phase I study of intracranial injection of NK-92/5.28.z (HER2.taNK) cells in patients with recurrent HER2-positive glioblastoma (Quilt 3.C001)

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Trial Acronym

CAR2BRAIN

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

The main objective of this clinical study is to evaluate the safety and tolerability of NK-92/5.28.z (HER2.taNK) 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.

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Organizational Data

  •   DRKS00013333
  •   2017/11/23
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  •   yes
  •   Approved
  •   269/17, Ethikkommission des Fachbereichs Humanmedizin der Johann-Wolfgang-Goethe-Universität Frankfurt am Main
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Secondary IDs

  •   2016-000225-39 
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Health Condition or Problem studied

  •   C71 -  Malignant neoplasm of brain
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Interventions/Observational Groups

  •   Intracranial application of NK-92/5.28.z (HER2.taNK), 1x10E7-1x10E8
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I
  •   Yes
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Primary Outcome

1.) To evaluate the safety and tolerability of NK-92/5.28.z cells expressing a transgenic chimeric antigen receptor (CAR) targeting HER2.
2.) Determination of the maximum tolerated dose (MTD) or maximum feasible dose (MFD).
3.) Determination of recommended phase 2 doses both for intraoperative injections only (RP2Diio) and repetitive injections (RP2Dri).
4.) Assessment of pharmacokinetics and pharmacodynamics.

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Secondary Outcome

1.) NK-92- and/or CAR 5.28.z-directed immune response.
2.) Immunological, radiological or histological signs of efficacy and tumor penetrating ability of NK-92/5.28.z.
3.) Objective response rate.
4.) Progression-free survival.
5.) Overall survival.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Actual
  •   2017/12/01
  •   30
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1.) Recurrent or refractory HER2-positive glioblastoma or its variant gliosarcoma in which a relapse surgery (partial or total) is being planned.
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).
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%.

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Exclusion Criteria

1.) Previous anti-angiogenic therapy e.g. with bevacizumab (Avastin).
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.

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Addresses

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    • Goethe-Universität Frankfurt am Main
    • Theodor-W.-Adorno-Platz 1
    • 60323  Frankfurt am Main
    • Germany
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    • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main
    • Mr.  Dr.  Michael  Burger 
    • Theodor-Stern-Kai 7
    • 60590  Frankfurt am Main
    • Germany
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    • Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main
    • Mr.  Dr.  Michael  Burger 
    • Theodor-Stern-Kai 7
    • 60590  Frankfurt am Main
    • Germany
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Sources of Monetary or Material Support

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    • NantKwest, Inc.
    • 9920 Jefferson Blvd
    • CA 90232  Culver City
    • United States
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    • LOEWE Center for Cell and Gene Therapy
    • 60590  Frankfurt
    • Germany
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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