Dendritic Cell Vaccine for Children and Adults With Sarcoma

NCT01803152 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 20110462
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcoma; Soft Tissue Sarcoma; Bone Sarcoma

Keywords

Metastatic Sarcoma; Relapsed Sarcoma; Dendritic Cell; Myeloid Derived Suppressor Cells; MDSC; MDSC Inhibition

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Measurement levels of Myeloid Derived Supressor Cells before and after treatment

  From Baseline to 3 Months Post-Treatment, up to 12 months

• Progression-free survival

  Up to 24 months Post-Treatment

• Overall Survival

  Up to 5 years Post-Treatment

• The rate of Complete Response (CR) or Partial Response (PR) in subjects receiving treatment

  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

Study Arms (2)

Part 1-DC Vaccine/Lysate

EXPERIMENTAL

* 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.

Biological: Dendritic Cells Vaccine; Biological: Lysate of Tumor; Drug: Imiquimod; Procedure: Leukapheresis

Part 2-Gemcitabine/DC Vaccine/Lysate

ACTIVE COMPARATOR

* 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.

Biological: Dendritic Cells Vaccine; Biological: Lysate of Tumor; Drug: Gemcitabine; Drug: Imiquimod; Procedure: Leukapheresis

Interventions

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.

Also known as: DC Vaccine

Part 1-DC Vaccine/Lysate; Part 2-Gemcitabine/DC Vaccine/Lysate

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.

Also known as: Lysate, Tumor Lysate

Part 1-DC Vaccine/Lysate; Part 2-Gemcitabine/DC Vaccine/Lysate

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.

Also known as: Gemzar

Part 2-Gemcitabine/DC Vaccine/Lysate

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.

Also known as: Aldara

Part 1-DC Vaccine/Lysate; Part 2-Gemcitabine/DC Vaccine/Lysate

Leukapheresis PROCEDURE

Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.

Also known as: Pheresis

Part 1-DC Vaccine/Lysate; Part 2-Gemcitabine/DC Vaccine/Lysate

Eligibility Criteria

• Age: 1 Year - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Serum Creatinine ≤ 1.5 X ULN
• Total Bilirubin ≤ 3 X ULN
• Albumin \> 2 g/dL
• 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.

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• Macarena De La Fuente, MD: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

Related Publications (1)

• 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.

  PMID: 35115306 DERIVED

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus; Gemcitabine; Imiquimod; Leukapheresis; Blood Component Removal

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Cytapheresis; Biological Therapy; Therapeutics; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Gina D'Amato, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 4, 2013
• Study Start: January 6, 2014
• Primary Completion: September 10, 2019
• Study Completion: June 21, 2024
• Last Updated: July 3, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)