Clinical Trials /

A Pilot Study of Glioma Associated Antigen Vaccines in Conjunction With Poly-ICLC in Pediatric Gliomas

NCT01130077

Description:

The overall objective of this pilot study is to collect immunological and safety data following administration of vaccinations with HLA-A2. This data will be used to decide whether a larger study of clinical efficacy is warranted.

Related Conditions:
  • Glioma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Pilot Study of Glioma Associated Antigen Vaccines in Conjunction With Poly-ICLC in Pediatric Gliomas
  • Official Title: A Pilot Study to Evaluate the Effects of Vaccinations With HLA-A2-Restricted Glioma Antigen-Peptides With Poly-ICLC for Children With Newly Diagnosed Malignant Brain Stem Gliomas, Non-Brainstem High-Grade Gliomas, Recurrent Low-Grade Gliomas or Recurrent High Grade Gliomas

Clinical Trial IDs

  • ORG STUDY ID: STUDY19040319
  • SECONDARY ID: PRO08030085
  • NCT ID: NCT01130077
  • NCT ALIAS: NCT00862199

Conditions

  • Newly Diagnosed Pediatric Pontine Glioma
  • Newly Diagnosed Pediatric High Grade Glioma
  • Recurrent Pediatric High Grade Glioma
  • Recurrent Pediatric Low Grade Glioma

Interventions

DrugSynonymsArms
HLA-A2 restricted glioma antigen peptides vaccineBB13624HLA Restricted glioma antigen peptides plus Poly ICLC
Poly-ICLCHLA Restricted glioma antigen peptides plus Poly ICLC

Purpose

The overall objective of this pilot study is to collect immunological and safety data following administration of vaccinations with HLA-A2. This data will be used to decide whether a larger study of clinical efficacy is warranted.

Trial Arms

NameTypeDescriptionInterventions
HLA Restricted glioma antigen peptides plus Poly ICLCExperimentalAll subjects will receive vaccine plus Poly ICLC will receive 9 injections ( once every 3 weeks)
  • HLA-A2 restricted glioma antigen peptides vaccine
  • Poly-ICLC

Eligibility Criteria

        **Inclusion Criteria

        *Tumor Types - Tumor type/location:

        Stratum A: Newly diagnosed diffuse intrinsic pontine gliomas OR any biopsy proven
        high-grade glioma* involving the brainstem. Patients may not have received chemotherapy
        during or after radiation. (Note: Stratum A is closed to accrual.)

        Stratum B: Newly diagnosed, non-brainstem high-grade glioma* Patients may not have received
        chemotherapy during or after radiation. (Note: Stratum B is open to accrual.)

        Stratum C: Unresectable low-grade gliomas that have received at least two
        chemotherapy/biologic regimens. Patients may not have received radiation to the index
        lesion within 1 year of enrollment. (Note: Stratum C is closed to accrual.)

        Stratum D: Non-brainstem high-grade gliomas* that have recurred following treatment. (Note:
        Stratum D is closed to accrual.)

        Stratum E: Newly diagnosed high-grade gliomas* or brain stem gliomas who received
        chemotherapy during radiation therapy. Patients may not have received chemotherapy after
        radiation therapy was completed. (Note: Stratum E is closed to accrual.)

        Stratum F: Newly diagnosed high-grade gliomas with metastatic disease within the CNS
        requiring craniospinal radiation therapy. Patients may or may not have received
        chemotherapy during radiation, but cannot have received chemotherapy after radiation
        therapy was completed. (Note: Stratum F is closed to accrual.)

          -  Eligible histologies include glioblastoma (GBM), anaplastic astrocytoma (AA) or
             gliosarcoma. Patients with any oligodendroglioma component are NOT eligible.

          -  HLA-A2 positive based on flow cytometry.

          -  Patients in Stratum A B and E must have received standard involved field radiation
             therapy [RT] defined as fractionated external beam radiotherapy with total doses
             between 5000-6000 cGy. Patients in these strata must be registered within 4-12 weeks
             of completing RT.

          -  Patients in Stratum F must have received craniospinal radiation.

          -  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.

          -  All patients must sign an IRB-approved informed consent document

          -  Patients must be ≥ 12 months and <22 years of age at the time of study registration.

          -  Patients must have a performance status of ≥ to 60.

          -  Patients must have life expectancy of at least 8 weeks.

          -  Documented negative serum βHCG for female patients who are post-menarchal. Pregnant
             females will not be included in the study. Males and females must agree to use
             effective birth control methods during the course of vaccination.

          -  Patients must be free of systemic infection.

          -  Patients with adequate organ function as measured by: Bone marrow: ANC > 1,000/µl;
             Platelets > 100,000/µl (transfusion independent); absolute lymphocyte count of
             ≥500/uL; 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 on Strata C and D must have recovered from the toxic effects of prior
             therapy: at least 3 weeks form 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.

        Presence of metastatic disease for patients in Stratum A, B, D and E. Patients with low
        grade gliomas (stratum C) may have tumor spread within the CNS.

        Patients in Stratum F must have tumor spread within the CNS.

        Patients enrolled in Strata A and B may not have received any prior chemotherapy or
        anti-glioma therapy of any type other than radiation therapy. Patients enrolled on stratum
        C must have received at least two prior chemotherapy or biologic therapy regimens and may
        not have received radiation to the index lesion within 1 year of enrollment. Patients on
        Strata A, B, E, and F can not have received chemotherapy after radiation therapy was
        completed.

        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.

        Use of immunosuppressives within four weeks prior to study entry. Dexamethasone, or other
        corticosteroid medications, if used in the peri-operative period and/or during
        radiotherapy, must be tapered (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.

        Patients with known addiction to alcohol or illicit drugs.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Tolerability during the first two vaccine courses as defined in the protocol.
Time Frame:6 weeks
Safety Issue:
Description:Tolerability during the first two vaccine courses as defined in the protocol.

Secondary Outcome Measures

Measure:Glioma-associated antigen-specific T-cell response
Time Frame:Monitoring will continue as long as subject remains on study.
Safety Issue:
Description:Glioma-associated antigen-specific T-cell response: determined by IFN-gamma-enzyme linked immune spot (ELISPOT) and tetramer assays

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Ian F. Pollack, M.D.

Trial Keywords

  • Pediatric glioma
  • Vaccine therapy

Last Updated

August 10, 2021