Vaccine Therapy and Poly-ICLC in Treating Younger Patients with Recurrent Low-Grade Gliomas that Cannot Be Removed by Surgery
This phase II trial studies how well vaccine therapy and polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC) work in treating younger patients with low-grade gliomas that have come back after treatment and cannot be removed by surgery. Vaccines made from peptides may help the body build an effective immune response to kill cancer cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer. Giving HLA-A2-restricted synthetic glioma antigen peptides vaccine and tetanus toxoid vaccine with poly-ICLC may work better in treating younger patients with recurrent low-grade gliomas that cannot be removed by surgery.
- 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); histologic confirmation of eligibility is required if tissue is available
- Human leukocyte antigen (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
- All patients must sign an Institutional Review Board (IRB)-approved informed consent document
- 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; 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; breastfeeding should be discontinued if the mother is treated in this study
- Patients must be free of systemic infection requiring intravenous (IV) antibiotics at the time of registration; patients must be off IV antibiotics for at least 7 days prior to registration
- Absolute neutrophil count (ANC) > 1,000/ul
- Platelets > 100,000/ul (transfusion independent)
- Absolute lymphocyte count of >= 500/uL
- Hemoglobin > 8 g/dl (may be transfused)
- Bilirubin < 1.5 x institutional normal for age
- Serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) < 3 x institutional normal
- Serum creatinine based on age or creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/ml/min/1.73 m^2
- Patients must have recovered from the toxic effects of prior therapy to grade 1 or better; patients must be 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
- 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, human immunodeficiency virus (HIV)-positive patients are excluded from the study
- Patients must be registered prior to the start of treatment
- The date protocol therapy is projected to start must be no later than 7 days after the date of study registration
Locations & Contacts
Contact: Gary E. Mason
Trial Objectives and Outline
I. Determine the efficacy of vaccination with tumor-associated antigen (TAA) peptides for children with recurrent low-grade gliomas, using objective measures of imaging-based tumor response and progression-free survival.
II. Characterize the rate and magnitude of immune response in post-vaccine peripheral blood mononuclear cells against vaccine peptides, in response to peptide-based vaccine therapy, using interferon (IFN)gamma-enzyme-linked immunosorbent spot (ELISPOT) and tetramer assays, and to correlate immunological response with clinical responses to the vaccine.
III. To further define the safety of the vaccine regimen in children with recurrent low-grade gliomas.
IV. Examine associations between antigen expression in the tumor and treatment response, and mechanisms of immune escape in tumors that progress after immunotherapy, issues that have not yet been systematically examined in these tumors.
Beginning week 0, patients receive HLA-A2-restricted synthetic glioma antigen peptides vaccine subcutaneously (SC), tetanus toxoid vaccine SC, and poly-ICLC intramuscularly (IM). Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
CONTINUATION THERAPY: Patients with evidence of tumor shrinkage or stable disease after initial 8 vaccines may receive additional HLA-A2-restricted synthetic glioma antigen peptides vaccine SC and tetanus toxoid vaccine SC every 6 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and annually for 2 years.
Trial Phase & Type
Children's Hospital of Pittsburgh of UPMC
Gary E. Mason
Secondary IDs NCI-2016-00644
Clinicaltrials.gov ID NCT02358187