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.
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
Interventions
Drug | Synonyms | Arms |
---|
NK-92/5.28.z | | NK-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
Name | Type | Description | Interventions |
---|
NK-92/5.28.z | Experimental | Intracranial application of NK-92/5.28.z, 1x10E7-1x10E8 | |
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
September 25, 2020