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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1-DC Vaccine/Lysate | Experimental |
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| Part 2-Gemcitabine/DC Vaccine/Lysate | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dendritic Cells Vaccine | Biological | Subjects will receive DC Vaccine administered once weekly, via intradermal injection, for 4 weeks for a total of four vaccinations, per study protocol. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | 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. | From Day 1 to 30 Days Post-Treatment, about 9 months |
| Measure | Description | Time Frame |
|---|---|---|
| Measurement levels of Myeloid Derived Supressor Cells before and after treatment | To explore biomarkers of immune response. Assessment will include measurement of levels of Myeloid Derived Supressor Cells before and after treatment and T and B cell subsets before and after treatment. | From Baseline to 3 Months Post-Treatment, up to 12 months |
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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)
Karnofsky/Lansky score of ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion.
Life expectancy of > 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.
Exclusion Criteria:
Pregnancy
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
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.
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| Name | Affiliation | Role |
|---|---|---|
| Gina D'Amato, MD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35115306 | Derived | Goff PH, Riolobos L, LaFleur BJ, Spraker MB, Seo YD, Smythe KS, Campbell JS, Pierce RH, Zhang Y, He Q, Kim EY, Schaub SK, Kane GM, Mantilla JG, Chen EY, Ricciotti R, Thompson MJ, Cranmer LD, Wagner MJ, Loggers ET, Jones RL, Murphy E, Blumenschein WM, McClanahan TK, Earls J, Flanagan KC, LaFranzo NA, Kim TS, Pollack SM. Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells. Clin Cancer Res. 2022 Apr 14;28(8):1701-1711. doi: 10.1158/1078-0432.CCR-21-4239. |
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| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D001859 | Bone Neoplasms |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C000706173 | lentiviral minigene vaccine of COVID-19 coronavirus |
| D000093542 | Gemcitabine |
| D000077271 | Imiquimod |
| D007937 | Leukapheresis |
| D001781 | Blood Component Removal |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| Lysate of Tumor | Biological | 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. |
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| Gemcitabine | Drug | Post-surgery, Leukapheresis and clearance of subject. Gemcitabine 1000 mg/m2 IV will be administered once weekly for 3 weeks per study protocol. |
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| Imiquimod | Drug | Subjects will self-apply Imiquimod topically to each designated vaccine site before and after scheduled administrations of DC Vaccine or Lysate, per study protocol. |
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| Leukapheresis | Procedure | Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained. |
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| Progression-free survival | To obtain preliminary clinical benefit by evaluating progression-free survival (PFS)in patients receiving this DC vaccine with or without gemcitabine pre-treatment. 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. | Up to 24 months Post-Treatment |
| Overall Survival | To obtain preliminary clinical benefit by evaluating overall survival in patients receiving this DC vaccine with or without gemcitabine pre-treatment. 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. | Up to 5 years Post-Treatment |
| The rate of Complete Response (CR) or Partial Response (PR) in subjects receiving treatment | To obtain preliminary clinical benefit by evaluating response rate (RR) in patients receiving this DC vaccine with or without gemcitabine pre-treatment. Response will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria, version 1.1. | Up to 24 months Post-Treatment |
| Measurement levels of Myeloid Derived Supressor Cells after Gemcitabine treatment | To determine if gemcitabine is effective in the inhibition and depletion of Myeloid Derived Supressor Cells in the study patients. | From Baseline to End of Treatment, about 10 months |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D016238 | Cytapheresis |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D047589 | Leukocyte Reduction Procedures |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D008919 | Investigative Techniques |