Clinical Trials /

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

NCT02960230

Description:

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.

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
  • Glioma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: H3.3K27M Peptide Vaccine for Children With Newly Diagnosed DIPG and Other Gliomas
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PNOC 007
  • SECONDARY ID: 150819
  • NCT ID: NCT02960230

Conditions

  • Diffuse Intrinsic Pontine Glioma
  • Glioma

Interventions

DrugSynonymsArms

Purpose

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.

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.

Trial Arms

NameTypeDescriptionInterventions
Newly Diagnosed DIPGExperimentalNewly 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.
    Newly Diagnosed Glioma (non-DIPG)ExperimentalNewly 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.

      Eligibility 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 (human leukocyte antigen A2)(CLIA approved laboratory)

      - The patient must have evaluable disease as defined in section 7.2.1.2

      - The patient must be either off 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 the standard pediatric dosing or dexamethasone is allowed.

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

      o Radiation therapy must have started within 28 days of diagnosis by imaging or surgery, whichever is later.

      - 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.

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

      - Patients with a history of auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible.

      Maximum Eligible Age:21 Years
      Minimum Eligible Age:3 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Number of Participants with Adverse Events related to treatment
      Time Frame:24 months
      Safety Issue:
      Description: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.

      Secondary Outcome Measures

      Measure: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
      Safety Issue:
      Description: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.

      Details

      Phase:Phase 1
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:University of California, San Francisco

      Trial Keywords

      • peptide vaccine
      • immunotherapy
      • DIPG
      • vaccine

      Last Updated

      November 9, 2016