Clinical trial NCT00766753: Vaccination-Dendritic Cells With Peptides for Recurrent Malignant Gliomas
Official title: A Phase I/II Evaluation of Vaccination With Type 1 Dendritic Cells Pulsed With Multiple Peptides in the Treatment of HLA-A2 Positive Patients With Recurrent Malignant Gliomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Glioma
Keywords: HLA-A2 positive
Malignant Gliomas
Vaccine
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Oncovir, Inc.
First posted: 2008-10-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: This is a single-institution Phase I/II study designed to evaluate the safety, the induction of an immune response, and the preliminary clinical response of vaccinations with Type-1 αDCs (αDC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. The hypothesis is that this form of vaccines in combination with poly-ICLC treatment will prove to be safe, and will induce potent anti-glioma immune responses.

The primary objective is to establish the safety of the approach.

The secondary objectives are to 1) 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) assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and four- and six-month progression-free survival (PFS).

Eligibility criteria: Inclusion Criteria:

* 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.
* Documented negative serum beta-HCG for female patients of child-bearing age.
* Patients must be free of systemic infection. 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.
* Patients must have adequate organ function as measured by:

  1. Hematopoietic:

     * granulocytes at least 2500/mm3
     * lymphocytes at least 1000/mm3
     * platelets at least 100,000/mm3
     * hemoglobin at least 10.0 g/dL
  2. Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be at least 50% or within the normal range of the institution. A cardiology clearance will be required for LV ejection fraction 50%.
  3. Hepatic: AST, ALT, GGT, LDH, Alk phos within 2.5 x upper normal limit and total bilirubin no greater than 2.0 mg/dL.
  4. Renal: Serum creatinine up to 1.5 x upper normal limit.
  5. Pretreatment baseline evaluations for laboratory parameters must be obtained within 10 to 18 days of subject registration.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants Who Experienced Treatment-related Dose Limiting Toxicities (DLT)
timeFrame: up to 8 weeks
measure: Median Time To Progression
timeFrame: At baseline, 9, 17, 25, and 33 weeks, and every 3 months; up to 23 months
Secondary outcomes:
measure: 12-month- Progression Free Survival (PFS)
timeFrame: Up to 12 months
measure: Overall Survival (OS)
timeFrame: Up to 102 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Frank Lieberman, MD
role: PRINCIPAL_INVESTIGATOR
References: