Clinical Trials /

A Vaccine Trial for Low Grade Gliomas

NCT02358187

Description:

The study will assess the immunogenicity, safety and preliminary clinical efficacy of the GAA/TT-peptide vaccine and poly-ICLC in HLA-A2+ children with unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. Radiation therapy counts as one biologic regimen, but patients may not have received radiation to the index lesion within 1 year of enrollment.

Related Conditions:
  • Glioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Vaccine Trial for Low Grade Gliomas
  • Official Title: A Phase II Study of Vaccinations With HLA-A2 Restricted Glioma Antigen Peptides in Combination With Poly-ICLC for Children With Recurrent Unresectable Low-Grade Gliomas (LGG)

Clinical Trial IDs

  • ORG STUDY ID: PRO13110086
  • SECONDARY ID: R01CA187219
  • NCT ID: NCT02358187

Conditions

  • Low Grade Glioma

Interventions

DrugSynonymsArms
Experimental: HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLCHLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC

Purpose

The study will assess the immunogenicity, safety and preliminary clinical efficacy of the GAA/TT-peptide vaccine and poly-ICLC in HLA-A2+ children with unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens. Radiation therapy counts as one biologic regimen, but patients may not have received radiation to the index lesion within 1 year of enrollment.

Detailed Description

      Patients will be treated with subcutaneous injections of GAA/TT-vaccines starting on Week 0
      and every 3 weeks thereafter for up to 8 cycles or until Off-treatment criteria are met
      (Section 4.6). I.m. poly-ICLC will be administered (30ug/kg i.m.) immediately following the
      vaccine. Poly-ICLC should be administered i.m. within 3 cm of the peptide-injection site.

      To allow for flexibility with scheduling, the peptide vaccine and Poly-ICLC dose may be given
      within one week of the date that the vaccine and poly-ICLC administration are due.

      Patients will be evaluated for any possible adverse event, regimen limiting toxicity (RLT) as
      well as clinical/radiological responses by clinical visits and MRI scanning. Follow-up MRIs
      will be performed (Weeks 6, 15 and 24).
    

Trial Arms

NameTypeDescriptionInterventions
HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLCExperimentalAll subjects will receive vaccine plus Poly-ICLC. Injections will be given every 3 week for a total of 8 vaccines.
  • Experimental: HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC

Eligibility Criteria

        Inclusion Criteria:

        Tumor Type

          -  Unresectable low-grade gliomas that have received at least two chemotherapy/biologic
             regimens. Radiation therapy counts as a biologic regimen. Patients may not have
             received radiation therapy to the index lesion within 1 year of enrollment. Patients
             may have tumor spread within the CNS.

          -  HLA-A2 positive based on flow cytometry.

          -  Patients must be clinically stable and off or on low-dose (no more than 0.1 mg/kg/day,
             max 4 mg/day Dexamethasone) corticosteroid for at least one week prior to study
             registration.

          -  Patients must be ≥ 12 months and < 22 years of age at the time of HLA-A2 screening.

          -  Patients must have a performance status of ≥ 70; (Karnofsky if > 16 years and Lansky
             if ≤ 16 years of age.

          -  Documented negative serum beta-HCG for female patients who are post-menarchal. Because
             the effect of the peptide-based vaccine and poly-ICLC on the fetus has not
             sufficiently been investigated, pregnant females will not be included in the study.

          -  Patients must be free of systemic infection requiring IV antibiotics at the time of
             registration. Patients must be off IV antibiotics for at least 7 days prior to
             registration.

          -  Patients with adequate organ function as measured by: Bone marrow: ANC > 1,000/µ;
             Platelets > 100,000/µ (transfusion independent); absolute lymphocyte count of ≥ 500/µ;
             Hemoglobin >8 g/dl (may be transfused). Hepatic: bilirubin < 1.5x institutional normal
             for age; SGPT (ALT) < 3x institutional normal.

          -  Renal: Serum creatinine based on age or Creatinine clearance or radioisotope GFR ≥ 70
             ml/min/ml/min/1.73 m²

          -  Patients must have recovered from the toxic effects of prior therapy to grade 1 or
             better. Patients must be at least 3 weeks from the last dose of standard cytotoxic
             chemotherapy or myelosuppressive biological therapy and at least 1 week from the last
             dose of non-myelosuppressive biologic therapy.

          -  No overt cardiac, gastrointestinal, pulmonary or psychiatric disease.

        Exclusion Criteria:

          -  Patients living outside of North America are not eligible.

          -  Patients may not have received radiation to the index lesion within 1 year of
             enrollment.

          -  Concurrent treatment or medications (must be off for at least 1 week) including:

               -  Interferon (e.g. Intron-A®)

               -  Allergy desensitization injections

               -  Growth factors (e.g. Procrit®, Aranesp®, Neulasta®)

               -  Interleukins (e.g. Proleukin®)

               -  Any investigational therapeutic medication

          -  Patients must not have a history of, or currently active autoimmune disorders
             requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with
             visceral involvement.

          -  Use of immunosuppressives within four weeks prior to study entry or anticipated use of
             immunosuppressive agents. Dexamethasone, or other corticosteroid medications, if used
             in the peri-operative period must be tapered to no more than 0.1 mg/kg/day, max 4
             mg/day dexamethasone for at least one week before study registration. Topical
             corticosteroids are acceptable.

          -  Because patients with immune deficiency are not expected to respond to this therapy,
             HIV-positive patients are excluded from the study.

          -  Patients who have received prior immunotherapy.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor shrinkage or stable disease
Time Frame:Week 24
Safety Issue:
Description:Participants who demonstrate radiological evidence of tumor shrinkage or stable disease without regimen-limiting toxicity (RLT) after the initial 8 vaccines will be eligible to receive additional vaccinations beginning week 24 and every 6 weeks thereafter for up to two years.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ian F. Pollack, M.D.

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