A Phase I Trial of Dendritic Cell Vaccination for Children and Adults With Sarcoma
Overview
- Phase
- Phase 1
- Intervention
- Dendritic Cells Vaccine
- Conditions
- Sarcoma
- Sponsor
- Macarena De La Fuente, MD
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
The purpose if this study is to evaluate an investigational vaccine using patient-derived dendritic cells (DC), a type of white blood cell that helps fight infections in the body, (DC) (a vaccine made out of participants' own cells and tumor) to treat sarcoma.
Investigators
Macarena De La Fuente, MD
Assistant Professor of Clinical
University of Miami
Eligibility Criteria
Inclusion Criteria
- •Age: 1 - 100 years old.
- •Histologically or cytologically confirmed sarcoma either relapsed or without known curative therapies. Both bone sarcomas and soft tissue sarcomas are eligible. Osteosarcoma, chondrosarcoma, Ewing's sarcoma and any other diagnoses of sarcoma are eligible as long as there is soft tissue that can be excised and be used to prepare lysate. Subjects presenting only with lesions that are only comprised of bone are excluded. Any number of prior therapies is allowed, including zero.
- •No radiotherapy to other sites planned and/or other chemotherapy planned for the study period. No radiotherapy or chemotherapy to have been received for at least 4 weeks before first vaccine administration. To allow for better local control without introducing undue toxicity into the trial, brachytherapy at time of surgery scheduled to end by one week before first vaccination is allowed if the radioactive source is to be removed (e.g. catheters can be placed if removable but implanted seeds are not allowed). In the event of positive margins being determined after surgical resection, but not determined in time for the placement of brachytherapy catheters, external beam radiotherapy may start after the last DC vaccination is administered but before the lysate boosts begin, and radiation must be planned to be complete before the first lysate boost.
- •No treatment with corticosteroids, antihistamines or salicylates for at least 1 week before first vaccination.
- •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 aminotransferase (AST)/Alanine transaminase (ALT) ≤ 2.5 X upper limit of normal (ULN); if liver metastases, ≤ 5 X ULN
Exclusion Criteria
- •Breast feeding females.
- •Any concomitant participation in other therapeutic trials
- •Virus serology known to be positive for HIV (testing is not required in the absence of clinical suspicion)
- •Documented immunodeficiency or autoimmune disease
- •Concomitant treatment with corticosteroids, antihistamines (H1 and H2 inhibitors) or salicylates. Patients may be eligible if the treatment is stopped at least 1 week before the first vaccination.
- •Brain metastases unless they have been stable for 3 months off of treatment directed specifically at them.
- •Known allergy to gemcitabine or its formulation components. Intolerant to gemcitabine
- •Does not apply to cohorts to be treated without gemcitabine
- •Prior therapy with gemcitabine is allowed on all cohorts
- •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.
Arms & Interventions
Part 1-DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Dendritic Cells Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 8, 12, 16 and 20; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Dendritic Cells Vaccine
Part 1-DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Dendritic Cells Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 8, 12, 16 and 20; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Lysate of Tumor
Part 1-DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Dendritic Cells Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 8, 12, 16 and 20; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Imiquimod
Part 1-DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Dendritic Cells Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 8, 12, 16 and 20; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Leukapheresis
Part 2-Gemcitabine/DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Gemcitabine: Post-Leukapheresis, administered once weekly for 3 weeks; * Dendritic Cells Vaccine (DC Vaccine): Post-Gemcitabine therapy, Recommended Phase 2 Dose (RP2D) administered once weekly for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 12, 16, 20 and 32; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Dendritic Cells Vaccine
Part 2-Gemcitabine/DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Gemcitabine: Post-Leukapheresis, administered once weekly for 3 weeks; * Dendritic Cells Vaccine (DC Vaccine): Post-Gemcitabine therapy, Recommended Phase 2 Dose (RP2D) administered once weekly for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 12, 16, 20 and 32; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Lysate of Tumor
Part 2-Gemcitabine/DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Gemcitabine: Post-Leukapheresis, administered once weekly for 3 weeks; * Dendritic Cells Vaccine (DC Vaccine): Post-Gemcitabine therapy, Recommended Phase 2 Dose (RP2D) administered once weekly for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 12, 16, 20 and 32; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Gemcitabine
Part 2-Gemcitabine/DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Gemcitabine: Post-Leukapheresis, administered once weekly for 3 weeks; * Dendritic Cells Vaccine (DC Vaccine): Post-Gemcitabine therapy, Recommended Phase 2 Dose (RP2D) administered once weekly for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 12, 16, 20 and 32; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Imiquimod
Part 2-Gemcitabine/DC Vaccine/Lysate
* Leukapheresis: Baseline, post-surgery; * Gemcitabine: Post-Leukapheresis, administered once weekly for 3 weeks; * Dendritic Cells Vaccine (DC Vaccine): Post-Gemcitabine therapy, Recommended Phase 2 Dose (RP2D) administered once weekly for 4 weeks; * Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 12, 16, 20 and 32; * Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Intervention: Leukapheresis
Outcomes
Primary Outcomes
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: From Day 1 to 30 Days Post-Treatment, about 9 months
To demonstrate that DC vaccination loaded with tumor lysate is feasible and that therapy with the vaccine with topical imiquimod (as final step in vaccine maturation), with or without the inhibition of MDSC by gemcitabine pre-treatment, is safe in pediatric and adult subjects with metastatic and refractory sarcoma.
Secondary Outcomes
- Measurement levels of Myeloid Derived Supressor Cells before and after treatment(From Baseline to 3 Months Post-Treatment, up to 12 months)
- The rate of Complete Response (CR) or Partial Response (PR) in subjects receiving treatment(Up to 24 months Post-Treatment)
- Overall Survival(Up to 5 years Post-Treatment)
- Progression-free survival(Up to 24 months Post-Treatment)
- Measurement levels of Myeloid Derived Supressor Cells after Gemcitabine treatment(From Baseline to End of Treatment, about 10 months)