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Trial record 2 of 76 for:    DIPG

H3.3K27M Peptide Vaccine for Children With Newly Diagnosed DIPG and Other Gliomas

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ClinicalTrials.gov Identifier: NCT02960230
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : July 9, 2018
Sponsor:
Collaborators:
The V Foundation for Cancer Research
Pacific Pediatric Neuro-Oncology Consortium
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:

This is a two cohort Phase I study within the Pacific Pediatric Neuro-Oncology Consortium (PNOC).

This study will assess the safety of repeated administration of the H3.3K27M specific vaccine in HLA-A2+ children and young adults with H3.3K27M DIPGs and other gliomas.


Condition or disease Intervention/treatment Phase
Diffuse Intrinsic Pontine Glioma Glioma Biological: K27M peptide Phase 1

Detailed Description:
Subjects who are eligible will receive a specific peptide vaccine, along with a helper drug called poly-ICLC, 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, now every 6 weeks, for a total of 96 weeks of treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: H3.3K27M Specific Peptide Vaccine Combined With Poly-ICLC for the Treatment of Newly Diagnosed HLA-A2+ H3.3K27M Positive Diffuse Intrinsic Pontine Glioma (DIPG) as Well as Other Newly Diagnosed HLA-A2+ H3.3K27M Positive Gliomas
Study Start Date : November 2016
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2020


Arm Intervention/treatment
Experimental: 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.
Biological: K27M peptide
K27M peptide vaccine, combined with Tetanus Toxoid peptide, emulsified in montanide. Poly-ICLC will be given concurrently

Experimental: 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.
Biological: K27M peptide
K27M peptide vaccine, combined with Tetanus Toxoid peptide, emulsified in montanide. Poly-ICLC will be given concurrently




Primary Outcome Measures :
  1. Number of Participants with Adverse Events related to treatment [ Time Frame: 24 months ]
    Safety of the vaccine 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 v4.0. 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. 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.


Secondary Outcome Measures :
  1. Induction of the H3.3K27M epitope-specific cytotoxic T lymphocyte (CTL) response in post vaccine peripheral mononuclear cells (PBMC) in HLA-A2+ children with DIPG and other gliomas [ Time Frame: 36 months ]
    A subject will be considered to have responded, if at any of post-vaccine time point against H3.3K27M antigen, the number of spots is double that at baseline, and there are at least 10 spots/20,000 cells, and if the number of the post-vaccine spots is at least three times the standard-deviation of the pre-vaccine value. This definition provides some protection against false positive response. We will correlate response with OS data. We will plot the time course of the magnitude of response and model it using a mixed-effects model approach.


Other Outcome Measures:
  1. Assess H3.3K27M expression status and infiltration of H3.3K27M specific T cells [ Time Frame: 36 months ]
    In subjects with evidence of progression that will undergo tissue collection as part of their standard of care, the tumor tissue will be analyzed for H3.3K27M expression status and infiltration of H3.3K27M specific T cells.

  2. Analyze circulating tumor DNA [ Time Frame: 36 months ]
    Archived tumor and normal DNA from each subject at time of initial diagnosis along with serial blood draw following therapy will be used for later studies to determine whether circulating tumor DNA (ctDNA) sequences in the subject's blood serve as biomarkers of tumor burden, response to therapy, or development of drug resistance.



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Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

The following eligibility criteria apply to both Stratum A and B.

  • The patient must test positive for HLA-A2 (tested by a CLIA approved laboratory; only the HLA A*02:01 subtype is eligible) 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.

    • 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.
  • H3.3K27 mutation must have been confirmed in the tumor tissue in a CLIA 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

  1. - 2 years 0.6 0.6
  2. 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 Neurologic Function Defined as:

  • Patients with seizure disorder may be enrolled if seizure disorder is well controlled.
  • The effects of the H3.3K27M vaccine on the developing human fetus are unknown. For this reason, females of child-bearing potential and men 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. Men 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 with a known disorder that affects their immune system, such as HIV, or an autoimmune 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
  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02960230


Contacts
Contact: Sabine Mueller, MD, PhD, MAS 877-827-3222 cancertrials@ucsf.edu
Contact: Lajhem Cambridge, MS 877-827-3222 cancertrials@ucsf.eduu

Locations
United States, California
Rady Children's Hospital-San Diego Recruiting
San Diego, California, United States, 92123
Contact: Jennifer Elster, MD    858-576-1600 ext 220040    jelster@rchsd.org   
Contact: John Crawford, MD    858-966-4939    jcrawford@rchsd.org   
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94158
Contact: Sabine Mueller, MD    415-476-3831    sabine.mueller@ucsf.edu   
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Lindsay Kilburn, MD    202-476-3854    lkilburn@cnmc.org   
Contact: Roger Packer, MD    202-476-5973    rpacker@cnmc.org   
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Stewart Goldman, MD    312-227-4873      
Contact: Rishi Lulla, MD    (312) 227-4874    RLulla@luriechildrens.org   
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Susan Chi, MD    617-632-4386    Susan_Chi@dfci.harvard.edu   
Contact: Daphne Haas-Kogan, MD    617-632-2291    Dhaas-kogan@lroc.harvard.edu   
United States, Minnesota
Children's Hospitals and Clinics of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Christopher Moertel, MD    612-626-2778    moert001@umn.edu   
Contact: Anne Bendel, MD    612-813-5940    anne.bendel@childrensmn.org   
United States, Missouri
St. Louis Children's Hospital Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Karen Gauvain, MD    314-454-2002    gauvain_k@kids.wustl.edu   
Contact: Joshua Rubin, MD, PhD    314-286-2790    rubin_j@kids.wustl.edu   
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Mohamed AbdelBaki, MD    614-722-4087    Mohamed.AbdelBaki@NationwideChildrens.org   
Contact: Jonathan Finlay, MD, MB, ChB, FRCP    614-722-4087    Jonathan.Finlay@nationwidechildrens.org   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Kellie Nazemi, MD    503-494-1543    nazemik@ohsu.edu   
Contact: Rebecca Loret de Mola, MD    503-494-1543    loretdem@ohsu.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jane Minturn, MD, PhD    267-426-5026    MINTURN@email.chop.edu   
Contact: Angela Waanders, MD       waandersa@email.chop.edu   
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Amar Gajjar, MD    901-595-2615    Amar.Gajjar@stjude.org   
Contact: Ibrahim Qaddoumi    901-595-2365    ibrahim.qaddoumi@stjude.org   
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Patricia Baxter, MD    832-824-4681    pabaxter@txch.org   
Contact: Donald W Parsons, MD, PhD    832-824-4643    dwparson@txch.org   
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Nicholas Whipple, MD, MPH    801-662-4700    nicholas.whipple@hsc.utah.edu   
Contact: Carol Bruggers    801-662-4700    Carol.bruggers@imail.org   
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Sarah Leary, MD    206-987-2106    sarah.leary@seattlechildrens.org   
Contact: Nicholas Vitanza, MD    206-987-2106    nicholas.vitanza@seattlechildrens.org   
Sponsors and Collaborators
University of California, San Francisco
The V Foundation for Cancer Research
Pacific Pediatric Neuro-Oncology Consortium
Investigators
Study Chair: Sabine Mueller, MD, PhD, MAS University of California, San Francisco
Study Chair: Hideho Okada, MD, PhD University of California, San Francisco

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02960230     History of Changes
Other Study ID Numbers: PNOC 007
150819 ( Other Identifier: University of California, San Francisco )
NCI-2017-01830 ( Other Identifier: Clinical Trials Reporting Program (CTRP) )
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: July 9, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of California, San Francisco:
peptide vaccine
immunotherapy
DIPG
vaccine

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vaccines
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Interferon Inducers