HLA-A2-Restricted Glioma Antigen-Peptides Vaccinations With Poly-ICLC for Recurrent WHO Grade II Gliomas

NCT00874861 | Completed Early Phase 1 DMC

• 2 other identifiers: 08-1351R21CA133859
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot vaccine study in adults with recurrent WHO Grade II gliomas. The purpose of this study is to test the safety and efficacy of an experimental tumor vaccine made from peptides in combination with the study drug Poly-ICLC. Poly-ICLC, manufactured by Oncovir, Inc., has already been received and is generally well tolerated by subjects in earlier studies and has been shown to decrease the size of brain tumors in some cases. The immunological and safety data will be used to decide whether a larger study of clinical efficacy is warranted.

Conditions

Astrocytoma; Oligoastrocytoma; Oligodendroglioma

Keywords

cancer; brain; tumor; vaccine

Outcome Measures

Primary Outcomes (1)

• Both immunological and safety data will serve as bases to decide whether a larger follow-up study is warranted.

  4 years

Secondary Outcomes (2)

• Clinical response: 6 month and 2-year progression-free survival (PFS) will be evaluated based on serial magnetic resonance imaging (MRI) scans.

  4 years

• Tumor tissues for biological correlates: for patients who develop progression, biopsy/resection will be encouraged and analyzed for GAA expression status and infiltration of GAA-specific T-cells

  4

Study Arms (1)

Vaccine + Poly-ICLC

EXPERIMENTAL

Peptide Vaccine + Poly-ICLC

Biological: Peptide vaccine + Poly-ICLC

Interventions

Peptide vaccine + Poly-ICLC BIOLOGICAL

Subcutaneously in right or left upper arms with intact draining axillary nodes. Each will be injected to the same location in the same arm as the previous vaccine was administered. In case of no intact axillary lymph nodes as draining nodes, vaccines will be administered in the upper thigh on the same side with intact inguinal lymph nodes. Vaccine will be administered on weeks 0,3,6,9,12,15,18 and 21. Poly-ICLC First course(20 mg/kg i.m., up to 1640 µg/injection) will be administered on an outpatient basis in the Clinical \& Translational Research Center (CTRC)the day of the first GAA/TT-vaccine and on day 4 after the vaccine. For each of the repeated vaccinations (on Weeks 3,6,9,12,15,18 and 21) poly-ICLC will be administered on day of the vaccine and on day 4 after the vaccine.

Vaccine + Poly-ICLC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have recurrent supratentorial WHO grade II astrocytoma, oligoastrocytoma or oligodendroglioma that is histologically confirmed either by the previous biopsy or resection, or at the time of re-operation (re-operation before entry to the current study is allowed; however post-surgery Decadron must be off for at least 4 weeks before administration of the first vaccine). Patients may have received prior external beam radiotherapy and/or chemotherapy. With regard to the prior therapy, patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy). The intent therefore is that patients may have had 3 prior therapies (initial therapy and treatment for 2 relapses). If the patient had a surgical resection for relapsed disease, and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse.
• HLA-A2 positive based on flow cytometry.
• Tumor recurrence is defined by the increase of maximum tumor diameter, based on the axial and/or coronal T2 or FLAIR MR images. Increase of tumor size can be based on comparison with previous scans performed up to prior 3 years to allow assessment of slow-growth of the tumor.
• Patients must have recovered from the toxic effects of prior therapy: 4 weeks from any investigational agent, 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 4 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Principal Investigator. With regard to previous RT, there must be at least 6 months from the completion of RT (or radiosurgery).
• Participants must be at least 18 years old. For patients under 18 years old, we have a separate, but similar vaccine study through the Children's Hospital in Pittsburgh.
• All participants must sign an informed consent document.
• Participants must have a Karnofsky performance status of \> 60 (Appendix I).
• Documented negative serum HCG for female participants of child-bearing age. Males and females must agree, in the consent form, to use effective birth control methods during the course of vaccination. 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.
• Participants must be free of systemic infection.
• Participants with adequate organ function as measured by white blood count ≥ 2500/mm3; lymphocytes ≥ 800/mm3; platelets ≥ 100,000/mm3, hemoglobin ≥ 10.0 g/dL, AST, ALT, GGT, LDH, alkaline phosphatase within 2.5 x upper normal limit, and total bilirubin ≤ 2.0 mg/dL, and serum creatinine within 1.5 X upper limit of normal limit. Coagulation tests PT and PTT have to be within normal limits.

You may not qualify if:

• Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease.
• Even if the initial diagnosis was WHO grade II glioma, if the pathological diagnosis for the recurrent disease demonstrate transformation to higher grade (i.e. WHO grade III or IV) gliomas, patients will be excluded from the eligibility.
• Concurrent treatment or medications including:
• Radiation therapy
• Chemotherapy
• Interferon
• Allergy desensitization injections
• Growth factors
• Interleukins
• Any investigational therapeutic medication
• Use of immunosuppressives within 4 weeks prior to study entry or anticipated use of immunosuppressive agents. Dexamethasone, or other corticosteroid medications, if used peri-operative period and/or during radiotherapy, must be tapered and discontinued at least 4 weeks before administration of the first vaccine. Topical corticosteroids and Inhaled steroids are acceptable.
• Participants who have another cancer diagnosis, except that the following diagnoses will be allowed:
• squamous cell cancer of the skin without known metastasis
• basal cell cancer of the skin without known metastasis
• carcinoma in situ of the breast (DCIS or LCIS)

Sponsors & Collaborators

• Ian F. Pollack, M.D.: lead
• Musella Foundation: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UPMC Hillman Cancer Center (University of Pittsburgh Cancer Institute)

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Neoplasms

Interventions

Protein Subunit Vaccines; poly ICLC

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Frank Lieberman, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Pediatric Neurosurgery

Study Record Dates

• First Submitted: April 2, 2009
• First Posted: April 3, 2009
• Study Start: April 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: November 1, 2013
• Last Updated: December 8, 2015

Record last verified: 2015-12

Locations

US (1)