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Dendritic Cell Vaccine for Children and Adults With Sarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01803152
Recruitment Status : Active, not recruiting
First Posted : March 4, 2013
Last Update Posted : July 19, 2021
Sponsor:
Information provided by (Responsible Party):
Macarena De La Fuente, MD, University of Miami

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.

Condition or disease Intervention/treatment Phase
Sarcoma Soft Tissue Sarcoma Bone Sarcoma Biological: Dendritic Cells Vaccine Biological: Lysate of Tumor Drug: Gemcitabine Drug: Imiquimod Procedure: Leukapheresis Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial of Dendritic Cell Vaccination for Children and Adults With Sarcoma
Actual Study Start Date : January 6, 2014
Actual Primary Completion Date : September 10, 2019
Estimated Study Completion Date : July 23, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Gemcitabine

Arm Intervention/treatment
Experimental: 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.
Biological: 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.
Other Name: DC Vaccine

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.
Other Names:
  • Lysate
  • Tumor Lysate

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.
Other Name: Aldara

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

Active Comparator: 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.
Biological: 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.
Other Name: DC Vaccine

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.
Other Names:
  • Lysate
  • Tumor Lysate

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

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.
Other Name: Aldara

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




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Measurement levels of Myeloid Derived Supressor Cells before and after treatment [ Time Frame: From Baseline to 3 Months Post-Treatment, up to 12 months ]
    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.

  2. Progression-free survival [ Time Frame: Up to 24 months Post-Treatment ]
    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.

  3. Overall Survival [ Time Frame: Up to 5 years Post-Treatment ]
    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.

  4. The rate of Complete Response (CR) or Partial Response (PR) in subjects receiving treatment [ Time Frame: Up to 24 months Post-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.

  5. Measurement levels of Myeloid Derived Supressor Cells after Gemcitabine treatment [ Time Frame: From Baseline to End of Treatment, about 10 months ]
    To determine if gemcitabine is effective in the inhibition and depletion of Myeloid Derived Supressor Cells in the study patients.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Year to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01803152


Locations
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United States, Florida
University of Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
Macarena De La Fuente, MD
Investigators
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Principal Investigator: Gina D'Amato, MD University of Miami
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Responsible Party: Macarena De La Fuente, MD, Assistant Professor of Clinical, University of Miami
ClinicalTrials.gov Identifier: NCT01803152    
Other Study ID Numbers: 20110462
First Posted: March 4, 2013    Key Record Dates
Last Update Posted: July 19, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Macarena De La Fuente, MD, University of Miami:
Metastatic Sarcoma
Relapsed Sarcoma
Dendritic Cell
Myeloid Derived Suppressor Cells
MDSC
MDSC Inhibition
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Imiquimod
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Adjuvants, Immunologic
Interferon Inducers