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Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors

Primary Purpose

Glioma, Brain Cancer, Brain Tumor

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dendritic Cell Vaccine

Tumor Lysate

Imiquimod

Leukapheresis

About this trial

This is an interventional treatment trial for Glioma focused on measuring Dendritic Cell Vaccine, DCV, Pediatric, Brain Tumor, In Situ, Lysate, Tumor Lysate, Glioblastoma Multiforme, GBM, Pheresis, Leukapheresis, High Grade Glioma, HGG

Eligibility Criteria

1 Year - 29 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age: ≥ 1 year and ≤ 29 years
Relapse or progression of any central nervous system tumor initially diagnosed before the age of 21 years.
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.
No radiotherapy and/or chemotherapy received for at least 1 month before first DC vaccination is to be administered.
No treatment with corticosteroids or salicylates for at least 1 week before first vaccination.
Life expectancy ≥ 3 months
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.
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
Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion.
Karnofsky score ≥ 70 or Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.

Exclusion Criteria:

Pregnancy.
Breast feeding females.
Any concomitant participation in other therapeutic trials.
Virus serology positive for HIV (testing is not required in the absence of clinical suspicion).
Documented immunodeficiency or autoimmune disease.
Other active malignancies.
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.
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.
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.

Sites / Locations

University of Miami

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DC Vaccine + Lysate

Arm Description

Leukapheresis: Baseline, post-surgery; Dendritic Cell Vaccine (DC Vaccine): Post-Leukapheresis, administered intradermally once weekly via intradermal injection, for 4 weeks for a total of four vaccinations; Tumor Lysate (Lysate): Post-DC Vaccine therapy. Administered intradermally during weeks 8, 12, 16, and 28; Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.

Outcomes

Primary Outcome Measures

Rate of Toxicity in Study Participants Receiving Protocol Therapy

Rate of treatment-limiting toxicities (TLT) and/or adverse events in study participants receiving protocol therapy.

Rate of Feasibility of Protocol Therapy in Study Participants

Rate of feasibility of protocol therapy in study participants. Feasibility refers to clinical feasibility - whether or not the patient can have enough monocytes removed to manufacture Dendritic Cells.

Secondary Outcome Measures

Rate of Prolonged Survival or Prolonged Progression-Free Survival in Study Participants

Rate of prolonged survival or prolonged progression-free survival in study participants. 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. 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.

Rate of Measurable Immune Response in Subjects Receiving Protocol Therapy.

Rate of measurable immune response in subjects receiving protocol therapy demonstrated by measurement levels of Myeloid Derived Suppressor Cells before and after treatment.

Comparison of clinical parameters of study participants versus associated outcomes for patients on other DC/Imiquimod studies.

A comparison of whether the clinical parameters associated with outcomes described for patients on other DC/Imiquimod protocols hold for subjects treated on this study.

Estimation of the Proportion of Subjects with Recurrent Pediatric Brian Tumors who are able to complete DC Vaccine therapy and DC Vaccine + Lysate Therapy.

Estimation of the proportion of subjects with recurrent pediatric brain tumors who are able to receive all administrations of DC, and the proportion who are able to receive all administrations of DC and Lysate.

Identification of Parameters Associated with Poorer Activity of the Vaccine in Study Participants

Identification of parameters associated with poorer activity of the DC Vaccine in Study Participants in order to develop therapies to augment vaccine therapy.

Full Information

NCT ID

NCT01902771

First Posted

July 16, 2013

Last Updated

March 8, 2017

Sponsor

Edward Ziga

1. Study Identification

Unique Protocol Identification Number

NCT01902771

Brief Title

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

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Terminated

Why Stopped

Lack of Accrual

Study Start Date

September 3, 2013 (Actual)

Primary Completion Date

October 24, 2016 (Actual)

Study Completion Date

January 26, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Edward Ziga

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DC Vaccine + Lysate

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Dendritic Cell Vaccine

Other Intervention Name(s)

DC Vaccine

Intervention Description

Post-Leukapheresis. Subjects will receive DC Vaccine administered once weekly, via intradermal injection, for 4 weeks for a total of four vaccinations, per study protocol.

Intervention Type

Biological

Intervention Name(s)

Tumor Lysate

Other Intervention Name(s)

Tumor Cell Lysate, Lysate of Tumor

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Imiquimod

Other Intervention Name(s)

Aldara

Intervention Description

Subjects will self-apply Imiquimod topically to each designated vaccine site before and after scheduled administrations of DC Vaccine or Lysate, per study protocol.

Intervention Type

Procedure

Intervention Name(s)

Leukapheresis

Other Intervention Name(s)

Pheresis

Intervention Description

Baseline, post-surgery. Subjects will undergo leukapheresis procedure during baseline, after recovery from surgery to collect peripheral blood mononuclear cells (PBMCs) from which dendritic cells will be obtained, per study protocol.

Primary Outcome Measure Information:

Title

Rate of Toxicity in Study Participants Receiving Protocol Therapy

Description

Rate of treatment-limiting toxicities (TLT) and/or adverse events in study participants receiving protocol therapy.

Time Frame

Up to 28 Weeks

Title

Rate of Feasibility of Protocol Therapy in Study Participants

Description

Time Frame

Up to 4 Weeks

Secondary Outcome Measure Information:

Title

Rate of Prolonged Survival or Prolonged Progression-Free Survival in Study Participants

Description

Time Frame

Up to 24 Months

Title

Rate of Measurable Immune Response in Subjects Receiving Protocol Therapy.

Description

Rate of measurable immune response in subjects receiving protocol therapy demonstrated by measurement levels of Myeloid Derived Suppressor Cells before and after treatment.

Time Frame

Up to 24 months

Title

Comparison of clinical parameters of study participants versus associated outcomes for patients on other DC/Imiquimod studies.

Description

A comparison of whether the clinical parameters associated with outcomes described for patients on other DC/Imiquimod protocols hold for subjects treated on this study.

Time Frame

Up to 24 Months

Title

Estimation of the Proportion of Subjects with Recurrent Pediatric Brian Tumors who are able to complete DC Vaccine therapy and DC Vaccine + Lysate Therapy.

Description

Time Frame

Up to 24 months

Title

Identification of Parameters Associated with Poorer Activity of the Vaccine in Study Participants

Description

Identification of parameters associated with poorer activity of the DC Vaccine in Study Participants in order to develop therapies to augment vaccine therapy.

Time Frame

Up to 24 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

29 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age: ≥ 1 year and ≤ 29 years Relapse or progression of any central nervous system tumor initially diagnosed before the age of 21 years. 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. No radiotherapy and/or chemotherapy received for at least 1 month before first DC vaccination is to be administered. No treatment with corticosteroids or salicylates for at least 1 week before first vaccination. Life expectancy ≥ 3 months 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. 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 Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion. Karnofsky score ≥ 70 or Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. Exclusion Criteria: Pregnancy. Breast feeding females. Any concomitant participation in other therapeutic trials. Virus serology positive for HIV (testing is not required in the absence of clinical suspicion). Documented immunodeficiency or autoimmune disease. Other active malignancies. 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. 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Edward Ziga, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

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Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors

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