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| Sponsor: | Children's Hospital of Pittsburgh |
|---|---|
| Collaborators: |
Stratum A,B and E NCI R21 CA149872 Stratum C-Brain Tumor Society Stratum D- P01NS40923 |
| Information provided by: | Children's Hospital of Pittsburgh |
| ClinicalTrials.gov Identifier: | NCT01130077 |
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.
| Condition | Intervention |
|---|---|
|
Newly Diagnosed Pediatric Pontine Glioma. Newly Diagnosed Pediatric High Grade Glioma. Recurrent Pediatric High Grade Glioma. Recurrent Pediatric Low Grade Glioma. |
Biological: HLA-A2 restricted synthetic glioma antigen peptides vaccine Drug: Poly ICLC Genetic: Reverse transcriptase-polymerase chain reaction Other: enzyme-linked immunosorbent assay Other: flow cytometry Other: immunohistochemisty staining method Other: laboratory biomarker analysis |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Pilot Study to Evaluate the Effects of Vaccinations With HLA-A2-Restricted Glioma Antigen-Peptides in Combination With Poly-ICLC for Children With Newly Diagnosed Malignant or Intrinsic Brain Stem Gliomas (BSG) or Non-Brainstem High-Grade Gliomas (HGG) or Recurrent Unresectable Low-Grade Gliomas (LGG) or Recurrent High Grade Gliomas |
| Estimated Enrollment: | 60 |
| Study Start Date: | February 2009 |
| Estimated Primary Completion Date: | February 2013 (Final data collection date for primary outcome measure) |
Eligibility| Ages Eligible for Study: | 19 Months to 20 Years |
| Genders Eligible for Study: | Both |
Inclusion Criteria:
3.1.1 Tumor Types - Tumor type/location:
Stratum A: Newly diagnosed diffuse intrinsic pontine gliomas OR any biopsy proven high-grade glioma* involving the brainstem
Stratum B: newly diagnosed, non-brainstem high-grade glioma* (i.e. definite residual tumor visible on imaging).
*Eligible histologies include glioblastoma (GBM), anaplastic astrocytoma (AA) or gliosarcoma. Patients with any oligodendroglioma component are NOT eligible.
Stratum C: Unresectable progressive low-grade gliomas that have recurred despite at least two chemotherapy/biologic treatment options. Patients may not have received radiation to the index lesion within 2 years of registration.
Stratum D: Recurrent high-grade gliomas* that have recurred following treatment. Patients must have recovered from the toxic effects of prior therapy: 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. Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator.
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. Patients must be registered within 4-12 weeks of completing radiation.
3.1.2 HLA-A2 positive based on flow cytometry.
3.1.3 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.
3.1.4 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.
3.1.5 All patients must sign an IRB-approved informed consent document
3.1.6 Patients must be greater than 18 months and less than 21 years of age at the time of study registration.
3.1.7 Patients must have a performance status of greater than or equal to 50; (Karnofsky if greater than 16 years and Lansky if less than 16 years of age.
3.1.8 Documented negative serum 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. Males and females must agree to use effective birth control methods during the course of vaccination (from the first vaccine to two weeks after the last vaccine). Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the peptide-based vaccine and poly-ICLC, breastfeeding should be discontinued if the mother is treated in this study.
3.1.9 Patients must be free of systemic infection at the time of registration. Subjects on IV antibiotic therapy must be off IV antibiotics for at least 7 days prior to registration.
3.1.10 Patients with adequate organ function as measured by: Bone marrow: ANC grater than 1,000/ul; Platelets greater than 100,000/ul (transfusion independent); Hemoglobin greater than 8 g/dl (may be transfused). Hepatic: bilirubin less than or equal to 1.5x institutional normal for age; SGPT (ALT) Less than 3x institutional normal and albumin greater than or equal to 2g/dl.
Renal: Serum creatinine based on age or Creatinine clearance or radioisotope GFR greater than 70 ml/min/1.73 m²
3.1.11 No overt cardiac, gastrointestinal, pulmonary or psychiatric disease.
3.1.12 For patients in stratum C, recovery from the effects of prior chemotherapy is required, as defined by the organ function criteria noted in 3.1.10.
-
Exclusion Criteria:
3.2.2 Patients enrolled in Stratum A and B may not have received any prior chemotherapy or anti-glioma therapy of any type other than radiation therapy (see 3.1.3) Patients enrolled on stratum C must have received at least two prior chemotherapy or biologic therapy regimens and/or radiation therapy. Patients may not have received radiation to the index lesion within 2 years of enrollment.
3.2.3 Concurrent treatment or medications (must be off for at least 1 week) including:
3.2.4 Patients must not have a history of, or currently active autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. The following will not be exclusionary:
• Mild arthritis requiring NSAID medications
3.2.5 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 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.
3.2.6 Patients with known addiction to alcohol or illicit drugs.
3.2.7 Because patients with immune deficiency are not expected to respond to this therapy, HIV-positive patients are excluded from the study.
Contacts and Locations| United States, Pennsylvania | |
| Children's Hospital of Pittsburgh of UPMC | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15224 | |
| Contact: Angela Krol, BSN 412-692-8047 angela.krol@chp.edu | |
| Principal Investigator: | Regina Jakacki, MD | Children's Hospital of Pittsburgh of UPMC |
More Information
| ClinicalTrials.gov Identifier: | NCT01130077 History of Changes |
| Obsolete Identifiers: | NCT00862199 |
| Other Study ID Numbers: | PRO08030085 |
| Study First Received: | May 24, 2010 |
| Last Updated: | June 28, 2011 |
| Health Authority: | United States: Food and Drug Administration |
|
Pediatric glioma Vaccine therapy |
|
Glioma Pontine Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial |
Neoplasms, Nerve Tissue Astrocytoma Poly ICLC Interferon Inducers Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |