Clinical trial NCT01795313: Immunotherapy for Recurrent Ependymomas in Children Using Tumor Antigen Peptides with Imiquimod
Official title: Immunotherapy for Recurrent Ependymomas in Children Using Human Leukocyte Antigen (HLA)-A2 Restricted Tumor Antigen Peptides in Combination with Imiquimod
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ependymoma
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Solving Kids' Cancer
name: National Cancer Institute (NCI)
First posted: 2013-02-20
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a pilot study to assess tolerability of our vaccine regimen in children with ependymomas initially arising above or below the tentorium
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if vaccination with HLA-A2 restricted peptides, combined with the immunoadjuvant imiquimod is safe and can induce immune responses in children with recurrent ependymomas. Eligible patients are stratiﬁed by primary tumor location.


Eligibility criteria: Inclusion Criteria: All grades of ependymoma are eligible.

* Patients must have recurrent/progressive ependymoma that has progressed or recurred after initial adjuvant therapy.
* HLA-A2 positive based on flow cytometry performed at the University of Pittsburgh.
* Patients must have previously received standard initial therapy including attempted gross total resection, where safely feasible, and in appropriate circumstances (e.g., those older than one year at initial diagnosis, with non-metastatic tumors and at least microscopic residual disease), involved field fractionated radiation therapy (RT). Patients may have received re-irradiation but not to the index lesion within 4 weeks.
* 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.
* Patients must be ≥ 12 months and \<22 years of age at the time of study registration.
* Patients must have a performance status of ≥ 70; (Karnofsky if \> 16 years and Lansky if ≤ 16 years of age).
* Patients may have non-bulky, asymptomatic metastatic disease.
* 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).
* Patients must be free of systemic infection requiring IV antibiotics at the time of registration and off IV antibiotics for at least 7 days prior to registration.
* Patients must have adequate organ function as measured by:

  * Bone marrow: Absolute neutrophil count (ANC) \> 1,000/µl; Platelets \> 100,000/µl (transfusion independent); Absolute lymphocyte count (ALC) ≥ 500/µl; Hemoglobin \>8 g/dl (may be transfused).
  * Hepatic: bilirubin ≤ 1.5x institutional normal for age; serum glutamate pyruvate transaminase (SGPT) \< 3x institutional normal
  * Renal: Serum creatinine based on age or creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70 ml/min/1.73 m²
* Patients must have recovered from the toxic effects of prior therapy and be at least 3 weeks from the last dose of standard cytotoxic chemotherapy or myelosuppressive biological therapy, at least one week from the last dose of non-myelosuppressive biological therapy and at least 4 weeks from the completion of radiation therapy.
* Patients must have no overt cardiac, gastrointestinal, pulmonary, or psychiatric disease.

Patients must be willing to travel to Pittsburgh to receive the vaccine. Visits: Every 3 weeks x 9, then every 6 weeks x 12 depending on response/side effects

Exclusion Criteria:

* Patients living outside of North America are not eligible.
* Patients must be off concurrent treatment or medications 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®), and any investigational therapeutic medication.
* Patients must not have a history of any immune system disorder or laboratory abnormality or any condition that could potentially alter immune function.
* Use of immunosuppressives within four weeks prior to study entry or anticipated use of immunosuppressive agents. Patients must be on 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.
* Patients with a known immune deficiency.
* Pregnancy or breastfeeding. Female patients who are post-menarchal must have a documented negative pregnancy test.
* Tetanus vaccine during therapy or within 1 week prior to enrollment.
* Patients who have received prior immunotherapy.

Primary outcomes:
measure: Number of Participants with unacceptable toxicity
timeFrame: 2 years
Secondary outcomes:
measure: Tumor-associated antigen-specific T-cell
timeFrame: 2 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: James Felker, MD
role: PRINCIPAL_INVESTIGATOR
References: