Clinical trial NCT01902771: Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors
Official title: A Phase I Study of Dendritic Cell Vaccine Therapy With In Situ Maturation for Pediatric Brain Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Glioma
Brain Cancer
Brain Tumor
Glioblastoma Multiforme
High Grade Glioma
Keywords: Dendritic Cell Vaccine
DCV
Pediatric
Brain Tumor
In Situ
Lysate
Tumor Lysate
Glioblastoma Multiforme
GBM
Pheresis
Leukapheresis
High Grade Glioma
HGG
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2013-07-18
Enrollment: 1
Sex: ALL
Minimum age (years): 1
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: DC vaccine manufactured and partially matured using our standard operating procedures, developed in collaboration with the HGG Immuno Group, then administered through imiquimod treated skin will be safe and feasible in children with refractory brain tumors. This will result in anti-tumor immunity that will prolong survival of subjects treated and results will be consistent with the outcomes found for subjects treated by HGG Immuno Group investigators. Study treatment will correlate with laboratory evidence of immune activation. Correlative studies will also reveal targets in the immune system which can be exploited to improve response for patients on successor trials.


Eligibility criteria: Inclusion Criteria:

1. Age: ≥ 1 year and ≤ 29 years
2. Relapse or progression of any central nervous system tumor initially diagnosed before the age of 21 years.
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 or 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.
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) ≥750/L
   * Lymphocytes ≥ 500/L
   * Platelets ≥ 75,000/L
   * Hemoglobin ≥ 9 g/dL
   * Aspartate aminotransferase (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 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. Other active malignancies.
7. 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.
8. 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.
9. 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.

Primary outcomes:
measure: Rate of Toxicity in Study Participants Receiving Protocol Therapy
timeFrame: Up to 28 Weeks
measure: Rate of Feasibility of Protocol Therapy in Study Participants
timeFrame: Up to 4 Weeks
Secondary outcomes:
measure: Rate of Prolonged Survival or Prolonged Progression-Free Survival in Study Participants
timeFrame: Up to 24 Months
measure: Rate of Measurable Immune Response in Subjects Receiving Protocol Therapy.
timeFrame: Up to 24 months
measure: Comparison of clinical parameters of study participants versus associated outcomes for patients on other DC/Imiquimod studies.
timeFrame: Up to 24 Months
measure: Estimation of the Proportion of Subjects with Recurrent Pediatric Brian Tumors who are able to complete DC Vaccine therapy and DC Vaccine + Lysate Therapy.
timeFrame: Up to 24 months
measure: Identification of Parameters Associated with Poorer Activity of the Vaccine in Study Participants
timeFrame: Up to 24 Months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Edward Ziga, MD
role: PRINCIPAL_INVESTIGATOR
References: