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SNCTP000004155 | NCT02960230 | BASEC2020-02310

Klinische Studie mit einem synthetischen Peptid zur Immunisierung gegen hochgradige, diffuse Mittellinien Gliome mit einer H3.3 Mutation bei Kindern und jungen Erwachsenen

Data source: BASEC (Imported from 27.01.2022), WHO (Imported from 18.01.2022)
Changed: 18.01.2022
Disease category: Head and Neck Cancer

Brief description of trial (Data source: BASEC)

Derzeit gibt es keine wirksamen Therapien für pädiatrische maligne Gliome.
Gliome, die innerhalb von Mittellinienstrukturen - wie es bei DIPG der Fall ist- liegen, haben eine besonders schlechte Prognose. Die Immuntherapie, wie z.B. aktive Impfungen, hat das Potenzial, sich zu einer wirksamen und sicheren Modalität für diese Patienten zu entwickeln. Es wird erwartet, dass Impfstoffe, die spezifische Peptide verwenden, im Vergleich zu ganzen Gliom-abgeleiteten Antigenen besser durchführbar sind, da diese Impfstoffe Gliom-spezifische Immunantworten induzieren können, ohne dass theoretische Bedenken hinsichtlich einer Autoimmunenzephalitis bestehen. Darüber hinaus können diese Impfstoffe dank der Verwendung von synthetischen Antigenpeptiden und Montanid ISA-51 "von der Stange" hergestellt werden. Die Verwendung modifizierter Peptide (Peptide, in denen Aminosäurereste aus der Wildtyp-Sequenz ersetzt werden) kann es uns ermöglichen, in ganzen Gliomzellen effizientere T-Zell-Antworten als natürliche Antigene zu induzieren. Auf der Grundlage kürzlich veröffentlichter Labordaten hat die Verabreichung von Poly-ICLC zusammen mit den synthetischen Peptiden die Induktion von antipeptidzytotoxischen T-Lymphozyten (CTL) und den Transfer von antigenspezifischen T-Zellen zu den Hirntumorstellen bemerkenswert verbessert.
Wir stellen die Hypothese auf, dass die Kombination der PD-1-Hemmung mit dem H3.3K27M-spezifischen Peptidimpfstoff die Aktivität des Peptidimpfstoffs verbessern wird, indem die Reaktion der peptidgeprimten T-Zellen gegen den Tumor verstärkt wird.

Health conditions investigated (Data source: BASEC)

Diffuses intrinsisches Stammhirn Gliom (DIPG)
Diffuses Mittellinien Gliom (DMG)

Health conditions (Data source: WHO)

Diffuse Intrinsic Pontine Glioma;Glioma;Diffuse Midline Glioma, H3 K27M-Mutant

Rare disease (Data source: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Wir werden eine multizentrische Studie zur Bewertung der Sicherheit und Immunaktivität eines synthetischen Peptid-Impfstoffs durchführen, der spezifisch für das in Kombination mit Poly-ICLC verabreichte H3.3.K27M-Epitop und dem PD-1-Inhibitor Nivolumab verabreichte H3.3.K27M-Epitop bei HLA-A2 (02:01)+ Kindern mit neu diagnostizierte DIPG oder andere Gliome der Mittellinie, die positiv für H3.3 sind.

Interventions (Data source: WHO)

Biological: K27M peptide;Drug: Nivolumab

Criteria for participation in trial (Data source: BASEC)

Neu diagnostizierte Kinder im Alter von 3-21 Jahren mit der Diagnose eines DIPG oder eines anderen Mittellinienglioms als DIPG (mit Ausnahme von Rückenmarksgliomen), die positiv für die H3.3K27M-Mutation sind, die einer Standard-Bestrahlungstherapie unterzogen wurde

Exclusion criteria (Data source: BASEC)

Patienten, die ein andere Prüfmedikation erhalten oder erhalten haben
Patienten, die einer Krebsbehandlung unterzogen wurden
Patienten mit einer Immunschwäche
Patienten mit einer Organ- oder Rückenmarkstransplantation
Schwangere oder stillende Frauen

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

- Stratum A:

• Newly diagnosed children (3-21 years old) with DIPG who are positive for the
H3.3K27M mutation (positive testing in Clinical Laboratory Improvement Amendments
(CLIA) laboratory) that underwent standard radiation therapy.

- Stratum B:

• Newly diagnosed children (3-21 years old) with diagnosis of glioma other than DIPG
who are positive for the H3.3K27M mutation (positive testing in CLIA laboratory)
including spinal cord gliomas that underwent standard radiation therapy.

- Stratum C:

- Newly diagnosed children 3-21 years of age with diagnosis of DIPG or midline
glioma other than DIPG (excluding primary spinal cord gliomas) who are positive
for the H3.3K27M mutation (positive testing from a CLIA or equivalent laboratory
required), that underwent standard radiation therapy.

The following eligibility criteria apply to strata A, B and C:

- The patient must test positive for HLA-A*02:01 (positive testing from a CLIA or
equivalent laboratory required; only the HLA A*02:01 subtype is eligible; other
subtypes are excluded)

- The patient must be either off systemic steroids or be on stable dose of dexamethasone
or equivalent (max 0.1 mg/kg/day; maximum 4mg/day) at time of enrollment.

- Patients must not have received any prior chemotherapy, immunotherapy or bone marrow
transplant for the treatment of their tumor. Prior use of temozolomide during
radiation at maximum of the standard pediatric dosing (defined as 90 mg/m^2/dose
continuously during radiation therapy for 42 days) or dexamethasone is allowed.

- Patients must have undergone radiation therapy and surgery as part of their standard
of care.

- Stratum A: Radiation therapy must have started within 4 weeks of diagnosis by
imaging or surgery, whichever is later.

- Stratum B: For subjects undergoing surgery for more extensive resection,
radiation therapy should be started within 4-6 weeks from surgery.

- Stratum C: Radiation therapy must have started within 4 weeks of diagnosis by
imaging or surgery, whichever is later. For subjects undergoing surgery for more
extensive resection, radiation therapy should be started within 4-6 weeks from
surgery.

- Karnofsky = 50 for patients = 16 years of age, and Lansky = 50 for patients < 16 years
of age (See Appendix A). Patients who are unable to walk because of paralysis, but who
are up in a wheelchair, will be considered ambulatory for the purpose of assessing the
performance score.

- The patient must have adequate organ function defined as

Adequate Bone Marrow Function Defined as:

- Peripheral absolute neutrophil count (ANC) = 1000/mm3 and

- Platelet count = 100,000/mm3 (transfusion independent, defined as not receiving
platelet transfusions for at least 7 days prior to enrollment).

Adequate Renal Function Defined as:

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) = 70 mL/min/1.73
m2 or

- A serum creatinine based on age/gender as follows:

Age Maximum Serum Creatinine (mg/dL) Male Female 3 to < 6 years 0.8 0.8 6 to < 10 years 1 1
10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4 The threshold creatinine values in this
table were derived from the Schwartz formula for estimating GFR utilizing child length and
stature data published by the Center for Disease Control (CDC).

Adequate Liver Function Defined as:

- Bilirubin (sum of conjugated + unconjugated) = 1.5 x upper limit of normal (ULN) for
age and

- serum glutamic-pyruvic transaminase (SGPT)/ alanine aminotransferase (ALT) = 110 U/L
and

- Serum albumin = 2 g/dL.

Adequate Pancreatic Function Defined as:

• Serum lipase = ULN at baseline.

Adequate Pulmonary Function Defined as:

• No evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency,
and a pulse oximetry of > 92% while breathing room air.

Adequate Neurologic Function Defined as:

- Patients with seizure disorder may be enrolled if seizure disorder is well controlled.

- The effects of the H3.3K27M vaccine and nivolumab on the developing human fetus are
unknown. For this reason, females of child-bearing potential and males must agree to
use adequate contraception. Adequate methods include: hormonal or barrier method of
birth control; or abstinence prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately. Males treated or enrolled on this protocol must also agree to use
adequate contraception prior to the study and for the duration of study participation.

- Ability to understand a written informed consent document, and the willingness to sign
it. Assent will be obtained when appropriate based on the subjects age.

Exclusion Criteria:

- Investigational Drugs

- Patients who are currently receiving another investigational drug are not
eligible.

- Prior treatment with another investigational drug.

- Anti-cancer Agents

- Patients who are currently receiving other anti-cancer agents are not eligible.

- Prior treatment with other anti-cancer agents.

- Patients who have received a live / attenuated vaccine within 30 days of first
treatment.

- Patients with evidence of disseminated or leptomeningeal disease.

- Patients with a known disorder that affects their immune system, such as HIV or
Hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or
immunosuppressive therapy are not eligible. Note: Patients that are currently using
inhaled, intranasal, ocular, topical or other non-oral or non-IV steroids are not
necessarily excluded from the study but need to be discussed with the study chair.

- Patients with a = Grade 2 hypothyroidism due to history of autoimmunity are not
eligible. (Note: Hypothyroidism due to previous irradiation or thyroidectomy will not
impact eligibility).

- Patients who have received prior solid organ or bone marrow transplantation are not
eligible.

- Patients with uncontrolled infection.

- Female patients of childbearing potential must not be pregnant or breast-feeding.
Female patients of childbearing potential must have a negative serum or urine
pregnan

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02960230

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT02960230

Further information on trial

Date trial registered

02.11.2016

Incorporation of the first participant

18.11.2016

Recruitment status

Recruiting

Academic title (Data source: WHO)

H3.3K27M Specific Peptide Vaccine Combined With Poly-ICLC With and Without PD-1 Inhibition Using Nivolumab for the Treatment of Newly Diagnosed HLA-A2 (02:01)+ H3.3K27M Positive Diffuse Intrinsic Pontine Glioma (DIPG) and Newly Diagnosed HLA-A2 (02:01)+ H3.3K27M Positive Gliomas

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 1/Phase 2

Primary end point (Data source: WHO)

Number of Participants with Adverse Events related to treatment;Overall survival (OS) at 12 months (OS12)

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Zurich

Countries (Data source: WHO)

Switzerland, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Dr. Nicolas Gerber
+41 44 266 3117
glioma@kispi.uzh.ch

Contact for general information (Data source: WHO)

Sabine Mueller, MD, PhD, MAS;Hideho Okada, MD, PhD;Rosemarie Dehesa
University of California, San Francisco
(415) 502-1600
Rosemarie.Dehesa@ucsf.edu

Contact for scientific information (Data source: WHO)

Sabine Mueller, MD, PhD, MAS;Hideho Okada, MD, PhD;Rosemarie Dehesa
University of California, San Francisco
(415) 502-1600
Rosemarie.Dehesa@ucsf.edu

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Sabine Mueller, MD, PhD

Additional sponsors (Data source: WHO)

The V Foundation for Cancer Research;Pacific Pediatric Neuro-Oncology Consortium;Bristol-Myers Squibb

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

24.11.2020

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2020-02310

Secondary ID (Data source: WHO)

150819
NCI-2017-01830
CA209-8TX
PNOC 007