Dendritic Cell Vaccine for Children and Adults With Sarcoma

NCT ID: NCT01803152

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-06
• Study Completion Date: 2024-06-21

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Dendritic Cells Vaccine

Intervention Type: BIOLOGICAL

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

Lysate of Tumor

Intervention Type: 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.

Imiquimod

Intervention Type: 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.

Leukapheresis

Intervention Type: PROCEDURE

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

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.

Group Type: ACTIVE_COMPARATOR

Dendritic Cells Vaccine

Intervention Type: BIOLOGICAL

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

Lysate of Tumor

Intervention Type: 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.

Gemcitabine

Intervention Type: DRUG

Post-surgery, Leukapheresis and clearance of subject. Gemcitabine 1000 mg/m2 IV will be administered once weekly for 3 weeks per study protocol.

Imiquimod

Intervention Type: 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.

Leukapheresis

Intervention Type: PROCEDURE

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

Interventions

Dendritic Cells Vaccine

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

Lysate of Tumor

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: BIOLOGICAL

Gemcitabine

Post-surgery, Leukapheresis and clearance of subject. Gemcitabine 1000 mg/m2 IV will be administered once weekly for 3 weeks per study protocol.

Intervention Type: DRUG

Imiquimod

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: DRUG

Leukapheresis

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

Intervention Type: PROCEDURE

Other Intervention Names

DC Vaccine; Lysate; Tumor Lysate; Gemzar; Aldara; Pheresis

Eligibility Criteria

Inclusion Criteria

1. Age: 1 - 100 years old.

2. 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.

3. 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.

4. No treatment with corticosteroids, antihistamines or salicylates for at least 1 week before first vaccination.

5. 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

6. Karnofsky/Lansky score of ≥ 70% or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

7. Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion.

8. Life expectancy of > 3 months.

9. 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

1. Pregnancy

2. Breast feeding females.

3. Any concomitant participation in other therapeutic trials

4. Virus serology known to be positive for HIV (testing is not required in the absence of clinical suspicion)

5. Documented immunodeficiency or autoimmune disease

6. 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.

7. Brain metastases unless they have been stable for 3 months off of treatment directed specifically at them.

8. 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

9. 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.

10. 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.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Macarena De La Fuente, MD

OTHER

Sponsor Role: lead

Responsible Party

Macarena De La Fuente, MD

Assistant Professor of Clinical

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gina D'Amato, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35115306 (View on PubMed)

Other Identifiers

20110462

Identifier Type: -

Identifier Source: org_study_id