Clinical Trials /

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

NCT03383978

Description:

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.

Related Conditions:
  • Glioblastoma
  • Gliosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intracranial Injection of NK-92/5.28.z Cells in Patients With Recurrent HER2-positive Glioblastoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: EudraCT 2016-000225-39
  • NCT ID: NCT03383978

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
NK-92/5.28.zNK-92/5.28.z

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
NK-92/5.28.zExperimentalIntracranial application of NK-92/5.28.z, 1x10E7-1x10E8
  • NK-92/5.28.z

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03.
Time Frame:24 weeks
Safety Issue:
Description:qPCR detection of NK-92/5.28.z in blood or CSF

Secondary Outcome Measures

Measure:NK-92- and/or CAR 5.28.z-directed immune response.
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Objective response rate.
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Progression-free survival.
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Overall survival.
Time Frame:24 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Johann Wolfgang Goethe University Hospital

Last Updated

May 14, 2019