Clinical trial NCT01803152: Dendritic Cell Vaccine for Children and Adults With Sarcoma
Official title: A Phase I Trial of Dendritic Cell Vaccination for Children and Adults With Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoma
Soft Tissue Sarcoma
Bone Sarcoma
Keywords: Metastatic Sarcoma
Relapsed Sarcoma
Dendritic Cell
Myeloid Derived Suppressor Cells
MDSC
MDSC Inhibition
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2013-03-04
Enrollment: 19
Sex: ALL
Minimum age (years): 1
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: From Day 1 to 30 Days Post-Treatment, about 9 months
Secondary outcomes:
measure: Measurement levels of Myeloid Derived Supressor Cells before and after treatment
timeFrame: From Baseline to 3 Months Post-Treatment, up to 12 months
measure: Progression-free survival
timeFrame: Up to 24 months Post-Treatment
measure: Overall Survival
timeFrame: Up to 5 years Post-Treatment
measure: The rate of Complete Response (CR) or Partial Response (PR) in subjects receiving treatment
timeFrame: Up to 24 months Post-Treatment
measure: Measurement levels of Myeloid Derived Supressor Cells after Gemcitabine treatment
timeFrame: From Baseline to End of Treatment, about 10 months
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Gina D'Amato, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.