JOURNAL ONKOLOGIE – STUDIE
H3.3K27M Peptide Vaccine With Nivolumab for Children With Newly Diagnosed DIPG and Other Gliomas
Rekrutierend
NCT-Nummer:
NCT02960230
Studienbeginn:
November 2016
Letztes Update:
19.05.2021
Wirkstoff:
K27M peptide, Nivolumab
Indikation (Clinical Trials):
Glioma
Geschlecht:
Alle
Altersgruppe:
Alle
Phase:
-
Sponsor:
Sabine Mueller, MD, PhD
Collaborator:
The V Foundation for Cancer Research, Pacific Pediatric Neuro-Oncology Consortium, Bristol-Myers Squibb,
Studienleiter
Study Chair
University of California, San Francisco
Study Chair
University of California, San Francisco
Kontakt
Kontakt:
Phone: 877-827-3222
E-Mail: cancertrials@ucsf.edu» Kontaktdaten anzeigen
Kontakt:
E-Mail: rosemarie.dehesa@ucsf.edu» Kontaktdaten anzeigen
Studienlocations
(3 von 15)
92123 San Diego
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Jennifer Elster, MD
Phone: 858-576-1600
Phone (ext.): 220040
E-Mail: jelster@rchsd.org
John Crawford, MD
Phone: 858-966-4939
E-Mail: jcrawford@rchsd.org» Ansprechpartner anzeigen
94158 San Francisco
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Sabine Mueller, MD
Phone: 415-476-3831
E-Mail: sabine.mueller@ucsf.edu» Ansprechpartner anzeigen
20010 Washington
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Lindsay Kilburn, MD
Phone: 202-476-3854
E-Mail: lkilburn@cnmc.org
Roger Packer, MD
Phone: 202-476-5973
E-Mail: rpacker@cnmc.org» Ansprechpartner anzeigen
60611 Chicago
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Angela Waanders, MD
Phone: 312-227-4873
Stewart Goldman, MD
Phone: (312) 227-4874» Ansprechpartner anzeigen
02215 Boston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Susan Chi, MD
Phone: 617-632-4386
E-Mail: Susan_Chi@dfci.harvard.edu
Daphne Haas-Kogan, MD
Phone: 617-632-2291
E-Mail: Dhaas-kogan@lroc.harvard.edu» Ansprechpartner anzeigen
55455 Minneapolis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Anne Bendel, MD
Phone: 612-813-5940
E-Mail: anne.bendel@childrensmn.org
Maggie Skrypek, MD
Phone: 612-813-5940
E-Mail: maggie.skrypek@childrensmn.org» Ansprechpartner anzeigen
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Karen Gauvain, MD
Phone: 314-454-2002
E-Mail: gauvain_k@kids.wustl.edu
Joshua Rubin, MD, PhD
Phone: 314-286-2790
E-Mail: rubin_j@kids.wustl.edu» Ansprechpartner anzeigen
43205 Columbus
United StatesSchwebend» Google-Maps
97239 Portland
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Linda Stork, MD
E-Mail: storkl@ohsu.edu
Matthew Miller, MD
Phone: 503-494-0963
E-Mail: milmatth@ohsu.edu» Ansprechpartner anzeigen
19104 Philadelphia
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Jane Minturn, MD, PhD
Phone: 267-426-5026
E-Mail: MINTURN@email.chop.edu
Kristina Cole, MD
E-Mail: colek@email.chop.edu» Ansprechpartner anzeigen
38105 Memphis
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Amar Gajjar, MD
Phone: 901-595-2615
E-Mail: Amar.Gajjar@stjude.org
Christopher Tinkle
Phone: 901-595-8735
E-Mail: Christopher.Tinkle@STJUDE.ORG» Ansprechpartner anzeigen
77030 Houston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Patricia Baxter, MD
Phone: 832-824-4681
E-Mail: pabaxter@txch.org
Donald W Parsons, MD, PhD
Phone: 832-824-4643
E-Mail: dwparson@txch.org» Ansprechpartner anzeigen
84112 Salt Lake City
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Nicholas Whipple, MD, MPH
Phone: 801-662-4700
E-Mail: nicholas.whipple@hsc.utah.edu
Carol Bruggers
Phone: 801-662-4700
E-Mail: Carol.bruggers@imail.org» Ansprechpartner anzeigen
98105 Seattle
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Sarah Leary, MD
Phone: 206-987-2106
E-Mail: sarah.leary@seattlechildrens.org
Nicholas Vitanza, MD
Phone: 206-987-2106
E-Mail: nicholas.vitanza@seattlechildrens.org» Ansprechpartner anzeigen
8032 Zürich
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Nicolas Gerber, MD
Phone: +41 44 266 31 17
E-Mail: PNOC_Regulatory@ucsf.edu
Stephanie Mathes, PhD
Phone: +41 44 266 3726» Ansprechpartner anzeigen
Studien-Informationen
Detailed Description:Subjects who are eligible will receive a specific peptide vaccine, along with a helper drug
called poly-ICLC, in combination with nivolumab, every 3 weeks for the first 6 months of
treatment. Subjects will be monitored routinely by laboratory assessments, physical
evaluation, vital signs, and MRI. Subjects who tolerate therapy well and have stable or
improved disease after 6 months of treatment can continue to receive treatment, nivolumab
continuing every 3 weeks but vaccine and poly-ICLC now every 6 weeks, for a total of 96 weeks
of treatment.
Ein-/Ausschlusskriterien
Inclusion Criteria:- Stratum A:
• Newly diagnosed children (3-21 years old) with DIPG who are positive for the
H3.3K27M mutation (positive testing in 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 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
(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.
o Stratum A: Radiation therapy must have started within 4 weeks of diagnosis by
imaging or surgery, whichever is later.
o Stratum B: For subjects undergoing surgery for more extensive resection, radiation
therapy should be started within 4-6 weeks from surgery.
o 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.
- H3.3K27 mutation must have been confirmed in the tumor tissue in a CLIA or equivalent
approved laboratory.
- 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) ≥ 70mL/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 CDC.
Adequate Liver Function Defined as:
- Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 x upper limit of normal (ULN) for
age and
- SGPT (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 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
pregnancy test prior to the start of therapy (as clinically indicated).
Studien-Rationale
Primary outcome:1. Number of Participants with Adverse Events related to treatment (Time Frame - 24 months):
Safety of the vaccine (Strata A and B) or vaccine in combination with nivolumab (Stratum C) will be assessed by monitoring for adverse events (AEs), scheduled laboratory assessments, vital signs, & physical examinations for subjects who receive the vaccination. The severity of toxicities will be graded according to the NCI CTCAE v5.0. AEs & clinically significant lab abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity & relationship to study drug(s). Grade 1 & 2 AEs will be summarized if related to study therapy. Descriptive statistics will be utilized to display the data on toxicity seen.
2. Overall survival (OS) at 12 months (OS12) (Time Frame - 36 months):
OS12 will be the clinical efficacy primary endpoint for Stratum A. Any eligible subject that receives at least one dose of the K27M/TT vaccine will be considered evaluable for clinical efficacy. For subjects who are still alive at 12 months, OS12 will be censored at the last contact date. OS will be estimated using the Kaplan-Meier method.
Studien-Arme
- Experimental: Stratum A: Newly Diagnosed DIPG
Newly diagnosed children with diffuse intrinsic pontine glioma who are positive for HLA-A2 and the H3.3K27M mutation that underwent radiation therapy will receive the specific H3.3K27M peptide vaccine, combined with the tetanus toxoid (TT) peptide, emulsified in Montanide. Poly-ICLC, which is a synthetic nucleic acid, will be given concurrently to improve the therapeutic effects of the vaccine. Vaccine will be given every 3 weeks for the first 24 weeks, then if there is stable or improved disease, will be given every 6 weeks for a total treatment period of 96 weeks. - Experimental: Stratum B: Newly Diagnosed Glioma (non-DIPG)
Newly diagnosed children with gliomas other than DIPG who are positive for HLA-A2 and the H3.3K27M mutation that underwent radiation therapy will receive the specific H3.3K27M peptide vaccine, combined with the tetanus toxoid peptide, emulsified in Montanide. Poly-ICLC, which is a synthetic nucleic acid, will be given concurrently to improve the therapeutic effects of the vaccine. Vaccine will be given every 3 weeks for the first 24 weeks, then if there is stable or improved disease, will be given every 6 weeks for a total treatment period of 96 weeks. - Experimental: Stratum C: Newly Diagnosed DIPG or other Midline Glioma
Newly diagnosed children with DIPG or other midline gliomas (excluding spinal cord tumors) who are positive for HLA-A2 (02:01) and the H3.3K27M mutation that underwent radiation therapy will receive the specific H3.3K27M peptide vaccine, combined with the tetanus toxoid peptide, emulsified in Montanide. Poly-ICLC, which is a synthetic nucleic acid, will be given concurrently to improve the therapeutic effects of the vaccine. Nivolumab will also be given via IV. Vaccine will be given every 3 weeks for the first 24 weeks, then if there is stable or improved disease, will be given every 6 weeks for a total treatment period of 96 weeks. Nivolumab will continue to be given every 3 weeks throughout all of treatment.
Geprüfte Regime
- K27M peptide:
K27M peptide vaccine, combined with Tetanus Toxoid peptide, emulsified in montanide. Poly-ICLC will be given concurrently - Nivolumab:
anti-PD1 monoclonal antibody
Quelle: ClinicalTrials.gov
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