Vaccination-Dendritic Cells With Peptides for Recurrent Malignant Gliomas

NCT00766753 | Completed Phase 1 Results DMC

• 3 other identifiers: 05-115NIH/NINDS/NCI1R21CA117152-01A2
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-institution Phase I/II study designed to evaluate the safety and induction of an immune response, and preliminary clinical response of vaccinations with Type-1 alpha-DCs (alpha-DC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Approximately 30 subjects will be enrolled in this study at UPMC/UPCI Hillman Cancer Center. The study participants in this trial will be HLA-A2 positive male or female adults over 18 years of age. The primary objective is to establish the safety of this approach. The endpoints will be to determine the maximum tolerated dose (MTD) of alpha-DC1 vaccines in combination with a fixed dose of poly-ICLC, using standard criteria and close clinical followups. The secondary objectives are 1) to assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays; and 2) to assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and 4- and 6-month progression-free survival (PFS).

Conditions

Malignant Glioma

Keywords

HLA-A2 positive; Malignant Gliomas; Vaccine

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Treatment-related Dose Limiting Toxicities (DLT)

  Number of participants who experienced treatment-related Dose Limiting Toxicities (DLT) at any dose level.

  up to 8 weeks

• Median Time To Progression

  Median number of months until disease progression. Tumor size was assessed using magnetic resonance imaging (MRI) scans with contrast enhancement to detect change from baseline.

  At baseline, 9, 17, 25, and 33 weeks, and every 3 months; up to 23 months

Secondary Outcomes (2)

• 12-month- Progression Free Survival (PFS)

  Up to 12 months

• Overall Survival (OS)

  Up to 102 months

Study Arms (1)

Single

EXPERIMENTAL

All consenting, eligible subjects receive the intervention

Biological: Dendritic vaccine pulsed with multiple peptides; Biological: The first booster vaccine phase:; Biological: The second booster vaccine phase:

Interventions

Dendritic vaccine pulsed with multiple peptides BIOLOGICAL

Subjects will receive four (4) injections of the vaccine into the lymph nodes. Injection is guided by ultrasonography. Subjects will receive the first cycle of vaccine in the right groin. Two weeks after the first vaccine, subjects receive the same vaccine at the left groin, followed by the 3rd and the 4th vaccines in the left and right armpits, respectively, with two-week intervals. Each injection contains 0.2cc (less than 1/20th of a teaspoon) of a saline solution containing the vaccine cell mixture.

Single

The first booster vaccine phase: BIOLOGICAL

This phase will begin at week 13. These subjects will be treated with additional vaccinations every 4 weeks to a maximum of 5 vaccine injections and, if poly-ICLC is available from the supplier starting on the day of the first additional vaccine and twice/week for 8 injections following each additional vaccine. If poly-ICLC supply is not available from the supplier, DC vaccines only will be given in the booster phases.

Single

The second booster vaccine phase: BIOLOGICAL

At week 33, following the completion of 5 additional vaccines, if participants demonstrate stable disease or positive clinical response, if poly-ICLC supply is still available, participants will be offered additional DC-vaccines and poly-ICLC treatment. The second phase booster vaccines can be continued as long as the patient shows continued positive response or stable disease (both radiological and clinically) with no major adverse events, and as long as funding is available for the study. DC vaccines in this phase will be administered every 6 months+/- 2 weeks. 2). Poly-ICLC at 10µg/kg and up to 1640 µg/injection will be administered intramuscularly (i.m.) on the day of each booster DC vaccine. Poly-ICLC will be administered weekly thereafter for twice (at one week and two weeks after each vaccine) (e.g. if the previous DC vaccine was administered on a Thursday, subsequent poly-ICLC will be administered on the next two Thursdays

Single

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed
• recurrent glioblastoma (GBM)
• anaplastic astrocytoma (AA)
• anaplastic oligodendroglioma (AO)
• anaplastic mixed oligoastrocytoma (AMO)
• other anaplastic glioma
• Patients must have received prior external beam radiotherapy and/or chemotherapy unless patients refused the options.
• 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).
• Patients must be HLA-A2 positive.
• All patients must sign an informed consent document indicating that they are aware of the investigational nature of this study.
• Patients must sign an authorization for the release of their protected health information.
• Patients must be \> 18 years old, and with a life expectancy \> 8 weeks. -Patients must have a Karnofsky performance status of \> 60.
• 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.
• Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
• Patients must not have any serious concurrent medical illness.

You may not qualify if:

• Pregnant or breast-feeding.
• Presence of metastatic disease.
• Active bacterial, viral or fungal infections. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
• Chemotherapy, biologic therapy or radiation therapy less than one month prior to study entry.
• History or presence of autoimmune disease.
• Use of immunosuppressives within 4 weeks prior to study entry or anticipated use of immunosuppressive agents. Minimum doses of corticosteroid (dexamethasone up to 4 mg/day) is permitted.
• Subjects with uncontrolled pain. -Subjects who have sensitivity to drugs to provide local anesthesia.

Sponsors & Collaborators

• Frank Lieberman: lead
• Oncovir, Inc.: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Related Links

• Online database of trials; this links the viewer to the UPMC website

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Frank Lieberman
• Organization: University of Pittsburgh Cancer Institute

liebermanf@upmc.edu

(412) 648-6507

Study Officials

• Frank Lieberman, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: June 23, 2008
• First Posted: October 6, 2008
• Study Start: December 1, 2006
• Primary Completion: September 1, 2009
• Study Completion: June 1, 2016
• Last Updated: February 7, 2018
• Results First Posted: May 11, 2017

Record last verified: 2018-01

Locations

US (1)