Malignant Glioma, Glioblastoma Multiforme, Anaplastic Astrocytoma, High Grade Glioma
Conditions
Keywords
HGG, Dendritic Cell Vaccine, DC Vaccine, Leukapheresis
Brief summary
The purpose of this research study is to evaluate an investigational vaccine using patent-derived dendritic cells (DC) to treat malignant glioma or glioblastoma.
Interventions
BIOLOGICALDendritic Cell Vaccine
Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.
BIOLOGICALTumor Lysate
Post-DC Vaccine therapy. Up to 1.5 mg of Lysate of tumor per dose administered via intradermal injection at intervals defined by study protocol.
DRUGImiquimod
5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate
PROCEDURELeukapheresis
Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.
Sponsors
Macarena De La Fuente, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age: ≥ 13 years and ≤ 99 years. 2. (2a) Relapse of high grade glioma (anaplastic astrocytoma World Health Organization (WHO) grade III or glioblastoma multiforme WHO grade IV), histologically proven at first stage of disease (radiological evidence for recurrence suffices); OR (2b) Relapse of glioma, which was grade II at initial diagnosis, but which is grade III or IV at relapse based on radiological or pathological criteria. 3. Total or subtotal resection of tumor mass, confirmed by assessment by the neurosurgeon and by postoperative MRI scan within 72 hours after surgery. The post-operative assessment should demonstrate residual tumor less than or equal to 2 cm\^3 as judged by surgeon and on MRI the tumor should only show linear contrast enhancement at the border of the resection cavity or nodule less than 2 cm\^3. 4. No radiotherapy and/or chemotherapy received for at least 1 month before first DC vaccination is to be administered 5. No treatment with corticosteroids or salicylates for at least 1 week before first vaccination. Corticosteroid therapy should be rapidly weaned within 1-2 weeks after surgery. 6. Life expectancy \> 3 months. 7. Written consent by patient or parent(s) (if patient is \< 18 years) on an institutional review board (IRB)-approved informed consent form prior to any study-specific evaluation. Assent is required from children as per University of Miami (UM) IRB guidelines. Subject must be capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent. 8. Adequate organ function (to be measured at enrollment) * Absolute neutrophil count (ANC) ≥ 0.75 10\*3/µl * Lymphocytes ≥ 0.5 10\*3/µl * Platelets ≥ 75 10\*3/µl * Hemoglobin ≥ 9 g/dL * Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 2.5 X upper limit of normal (ULN); if liver metastases, ≤ 5 X ULN * Serum Creatinine ≤ 1.5 X ULN * Total Bilirubin ≤ 3 X ULN * Albumin \> 2 g/dL 9. Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion. 10. Karnofsky score 70 or higher or Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.
Exclusion criteria
1. Pregnancy. 2. Breast feeding females. 3. Any concomitant participation in other therapeutic trials. 4. Virus serology positive for HIV (testing is not required in the absence of clinical suspicion). 5. Documented immunodeficiency or autoimmune disease. 6. Mandatory treatment with corticosteroids or salicylates in the week prior to first vaccination. 7. Other active malignancies. 8. Patients with unresectable tumors, for instance pontine gliomas, are excluded. 9. Refusal to use adequate contraception for fertile patients (females and males) during the study and for 30 days after the last dose of study treatment. 10. Any serious or uncontrolled medical or psychiatric condition that in the opinion of the investigator makes the patient not able to participate in the study. 11. Application of gliadel wafers within the prior 4 months or a plan to place gliadel wafers at the time of resection for tumor acquisition for study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-Related Adverse Events | Up to Week 32 (30 days after last dose of protocol therapy) | Adverse Events will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 by treating physician |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Progression-Free Survival (PFS) in Study Participants | Up to Week 80 (5 years post therapy) | Rate of prolonged progression-free survival in study participants receiving protocol therapy. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status. |
| Change in MDSC Levels | Baseline, Up to Week 28 | Immune response will be reported as the change in Myeloid Derived Suppressor Cell (MDSC) levels from blood samples |
| Rate of Overall Survival (OS) in Study Participants | Up to Week 80 (5 years post therapy) | Rate of overall survival in study participants receiving protocol therapy. Overall survival is defined as the time elapsed from the start of treatment until death. For surviving patients, follow-up will be censored at the date of last contact. |
| Comparison of clinical parameters associated with outcomes in study participants to patients on other DC/Imiquimod studies. | Up to 5 years Post-Therapy | To demonstrate if the clinical parameters associated with outcomes described for patients on other DC / imiquimod protocols hold for subjects treated on this study. |
| Proportion of participants completing intervention. | Up to Week 28 | Proportion of participants able to receive all administrations of DC vaccine and those who are able to receive all administration of DC vaccine and lysate will be reported. |
| Change in blood counts | Baseline, Up to Week 28 | Measurement of immune response will be reported as the change in red and white blood counts from blood samples evaluated in million cells/microliter |
Countries
United States
Outcome results
None listed