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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Musella Foundation
Information provided by (Responsible Party):
Ian F. Pollack, M.D., University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00874861
First received: April 2, 2009
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Astrocytoma
Oligoastrocytoma
Oligodendroglioma
Biological: Peptide vaccine + Poly-ICLC
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
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 Adults With Recurrent WHO Grade II Gliomas

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Both immunological and safety data will serve as bases to decide whether a larger follow-up study is warranted. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Clinical response: 6 month and 2-year progression-free survival (PFS) will be evaluated based on serial magnetic resonance imaging (MRI) scans. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 4 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: April 2009
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine + Poly-ICLC
Peptide Vaccine + Poly-ICLC
Biological: Peptide vaccine + Poly-ICLC

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.


Detailed Description:

This is a pilot study of a vaccination regime that is designed to efficiently induce anti-tumor T-cell responses in patients with recurrent WHO grade II glioma. The proposed regime combines subcutaneous injections of glioma-associated antigen (GAA)-derived cytotoxic T-lymphocyte (CTL) epitope-peptides with simultaneous intramuscular (i.m.) administration of poly-ICLC.

The overall objective of this pilot study is to collect immunological and safety data that will be used to decide whether a larger study of clinical efficacy is warranted in these patients. All patients on the study will be followed for a minimum of 2 years, so that the actual 2-year overall survival (OS), 6-month and 2-year progression-free survival (PFS) rates can be determined in an exploratory manner.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. HLA-A2 positive based on flow cytometry.
  3. 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.
  4. 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).
  5. 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.
  6. All participants must sign an informed consent document.
  7. Participants must have a Karnofsky performance status of > 60 (Appendix I).
  8. 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.
  9. Participants must be free of systemic infection.
  10. 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.

Exclusion Criteria:

  1. Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease.
  2. 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.
  3. Concurrent treatment or medications including:

    • Radiation therapy
    • Chemotherapy
    • Interferon
    • Allergy desensitization injections
    • Growth factors
    • Interleukins
    • Any investigational therapeutic medication
  4. Participants must not have had prior autoimmune disorders requiring cytotoxic or immunosuppressive therapy, or autoimmune disorders with visceral involvement. Participants with an active autoimmune disorder requiring these therapies are also excluded. Mild arthritis requiring NSAID medications will not be exclusionary.
  5. 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.
  6. 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)
    • carcinoma in situ of the cervix
    • any cancer without distant metastasis that has been treated successfully, without evidence of recurrence or metastasis for over 5 years
  7. Participants with known addiction to alcohol or illicit drugs.
  8. Because patients with immune deficiency are not expected to respond to this therapy, HIV-positive patients are excluded from the study.
  9. Patients who previously participated in UPCI 07-057 are excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874861

Locations
United States, Pennsylvania
UPMC Hillman Cancer Center (University of Pittsburgh Cancer Institute)
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Ian F. Pollack, M.D.
Musella Foundation
Investigators
Principal Investigator: Frank Lieberman, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Ian F. Pollack, M.D., Chief, Pediatric Neurosurgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00874861     History of Changes
Other Study ID Numbers: 08-135, 1R21CA133859
Study First Received: April 2, 2009
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
cancer
brain
tumor
vaccine

Additional relevant MeSH terms:
Astrocytoma
Oligodendroglioma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Poly ICLC
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014