Summary

for people ages 3-21 (full criteria)
at San Francisco, California and other locations
study started
estimated completion:
Sabine Mueller Hideho Okada

Description

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.

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

Details

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.

Keywords

Diffuse Intrinsic Pontine Glioma Glioma peptide vaccine immunotherapy DIPG vaccine Vaccines Poly ICLC K27M peptide Newly Diagnosed DIPG Newly Diagnosed Glioma (non-DIPG)

Eligibility

You can join if…

Open to people ages 3-21

  • 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/m2/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

    • 2 years 0.6 0.6
  1. 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.

You CAN'T join if...

  • 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).

Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center accepting new patients
    San Francisco California 94158 United States
  • Rady Children's Hospital-San Diego accepting new patients
    San Diego California 92123 United States
  • University of Utah accepting new patients
    Salt Lake City Utah 84112 United States
  • Oregon Health & Science University accepting new patients
    Portland Oregon 97239 United States
  • Seattle Children's Hospital accepting new patients
    Seattle Washington 98105 United States
  • Texas Children's Hospital accepting new patients
    Houston Texas 77030 United States
  • Children's Hospitals and Clinics of Minnesota accepting new patients
    Minneapolis Minnesota 55455 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT02960230
Phase
Phase 1
Lead Scientists
Sabine Mueller
Hideho Okada
Study Type
Interventional
Last Updated
July 6, 2018