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New vaccine trial opens for pediatric (ages 3 to 20) high grade, low grade and brainstem glioma


Posted on: 03/16/2009

Phase I Pilot Study of HLA-A2-Restricted Synthetic Glioma Antigen Peptide Vaccine and Poly ICLC Vaccine in Young Patients With Newly Diagnosed Malignant or Intrinsic Brain Stem Glioma, Incompletely Resected Non-Brainstem High-Grade Glioma, or Recurrent Unresectable Low-Grade Glioma

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
 

Alternate Title

Vaccine Therapy in Treating Young Patients With Newly Diagnosed or Recurrent Glioma

 

Basic Trial Information

Phase
Type
Status
Age
Sponsor
Protocol IDs

Phase I

 

Biomarker/Laboratory analysis, Treatment

 

Approved-not yet active

 

3 to 20

 

Other

 

CHP-PRO08030085
PRO08030085

 

Objectives

Primary

  1. Determine the response rate and magnitude of immune response in patients with newly diagnosed malignant or intrinsic brain stem glioma, incompletely resected non-brainstem high-grade glioma, or recurrent unresectable low-grade glioma receiving HLA-A2-restricted synthetic glioma antigen peptides vaccine and poly ICLC vaccine.
  2. Assess the incidence and severity of adverse events associated with this regimen in these patients.

Secondary

  1. Determine the radiological/clinical response of patients treated with this regimen.
  2. Determine the overall and progression-free survival of patients treated with this regimen.
  3. Determine the biological correlates of expression of glioma-associated antigen (GAA) and infiltration of GAA-specific T-cells.

Entry Criteria

Disease Characteristics:

  • Diagnosis of 1 of the following:
    • Stratum A: Newly diagnosed diffuse intrinsic pontine glioma OR any biopsy-proven high-grade glioma* involving the brainstem
      • Must have received standard fractionated external beam radiotherapy (FEBRT) with total doses between 5,000-6,000 cGy within the past 4-12 weeks
      • No prior chemotherapy or anti-glioma therapy
      • No oligodendroglioma
      • No leptomeningeal metastatic disease
    • Stratum B: Newly diagnosed, incompletely resected, non-brainstem high-grade glioma* (i.e., definite residual tumor visible on imaging)
      • No oligodendroglioma
      • Must have received standard FEBRT with total doses between 5,000-6,000 cGy
      • No prior chemotherapy or anti-glioma therapy
      • No leptomeningeal metastatic disease
       [Note: *Eligible histologies include glioblastoma, anaplastic astrocytoma, and gliosarcoma]
    • Stratum C: Unresectable, progressive low-grade glioma of any subtype that has recurred despite 2 prior chemotherapy or biological therapy regimens and/or radiation therapy
      • Must have received ≥ 2 prior chemotherapy, biological therapy, and/or radiotherapy regimens
      • Recovered from prior chemotherapy
      • Leptomeningeal spread allowed


     
  • HLA-A2 positive based on flow cytometry

     
  • Must be clinically stable with or without low-dose (no more than 0.1 mg/kg/day, max 4 mg/day dexamethasone) corticosteroid for ≥ 1 week before study registration

     
  • No gross totally resected tumors (i.e., tumors with no definite visible residual disease by MRI)

     

 

Prior/Concurrent Therapy:

  • See Disease Characteristics
  • See Patient Characteristics
  • At least 7 days since prior antibiotic therapy
  • No concurrent treatment with any of the following:
    • Interferon
    • Chemotherapy
    • Allergy desensitization injections
    • Inhaled or parenteral steroids
      • Topical corticosteroids allowed
    • Growth factors
    • Interleukins
    • Any investigational therapeutic medication
    • Illicit drugs
  • At least 4 weeks since prior and no concurrent immunosuppressive therapies
    • At least 1 week since prior dexamethasone or other corticosteroid medications (if used in the peri-operative period and/or during radiotherapy) and must be tapered within 1 week before study therapy

 

Patient Characteristics:

  • Karnofsky/Lansky performance status 50-100% (for patients > 16 years of age)
  • ANC > 1,000/mm3
  • Platelet count > 100,000/mm3
  • Hemoglobin > 8 g/dL (transfusion allowed)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT < 3 times ULN
  • Albumin ≥ 2 g/dL
  • Creatinine clearance or radioisotope GFR > 70 mL/min OR serum creatinine based on age as follows:
    • 0.8 mg/dL (for patients 2 to < 6 years of age)
    • 1.0 mg/dL (for patients 6 to < 10 years of age)
    • 1.2 mg/dL (for patients 10 to < 13 years of age)
    • 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to < 16 years of age)
    • 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
  • PT and PTT normal for age
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No systemic infection
  • No overt cardiac, gastrointestinal, pulmonary, or psychiatric disease
  • No history of or currently active autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement
    • Mild arthritis requiring NSAID medications allowed
  • No known addiction to alcohol or illicit drugs

 

Expected Enrollment

36

Outcomes

Primary Outcome(s)

Immune response rate against glioma-associated antigen (GAA) peptides by ELISPOT, IHC, and reverse transcriptase-PCR
Adverse events as assessed by NCI CTCAE v.3.0
 

Secondary Outcome(s)

Clinical response (complete or partial response or stable disease)
Overall and progression-free survival
Correlation between GAA expression and GAA-specific T-cells infiltration
 

Outline

Patients are stratified according to tumor type and location: Stratum A (newly diagnosed malignant or intrinsic brain stem glioma) vs Stratum B (incompletely resected non-brainstem high-grade glioma) vs Stratum C (recurrent unresectable low-grade glioma).

Patients in stratum A and stratum B begin treatment 4-12 weeks after fractionated external beam radiotherapy (FEBRT) given off study.

All patients receive HLA-A2-restricted synthetic glioma antigen-peptides vaccine subcutaneously and poly ICLC vaccine intramuscularly. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response or stable disease may receive additional peptide and poly-ICLC vaccinations beginning 6 weeks after the 8th vaccination and continuing every 6 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and weeks 7, 16, and 25 for glioma-associated antigen (GAA) expression and GAA-specific T-cell-response analysis by ELISPOT assay. Tissue samples are collected either at baseline (pre-vaccines), after progression (post-vaccines), or both for GAA expression analysis by immunohistochemistry and reverse transcriptase-PCR assays. Tumor-infiltrated leukocytes are evaluated pre- and post-therapy via flow cytometry.

Trial Contact Information

Trial Lead Organizations

Children's Hospital of Pittsburgh

Regina Jakacki, MD, Principal investigator
Ph: 412-692-7056
Email: regina.jakacki@chp.edu


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