Description:
The study will assess the immunogenicity, safety and preliminary clinical efficacy of the
glioma associated antigen (GAA)/tetanus toxoid (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.
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:
STUDY19060121
- SECONDARY ID:
R01CA187219
- SECONDARY ID:
PRO13110086
- NCT ID:
NCT02358187
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Experimental: HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC | | HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC |
Purpose
The study will assess the immunogenicity, safety and preliminary clinical efficacy of the
glioma associated antigen (GAA)/tetanus toxoid (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
Name | Type | Description | Interventions |
---|
HLA-A2 Restricted Glioma Antigen-Peptides with Poly-ICLC | Experimental | All 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 central nervous system (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-human chorionic gonadotropin (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: absolute neutrophil
count (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; serum glutamate pyruvate transaminase
(SGPT) < 3x institutional normal.
- Renal: Serum creatinine based on age or Creatinine clearance or radioisotope
glomerular filtration rate (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. |
Last Updated
August 5, 2021