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A Phase I Trial of Dendritic Cell Vaccination With and Without Inhibition of Myeloid Derived Suppressor Cells by Gemcitabine Pre-Treatment For Children And Adults With Sarcoma

Phase 1
1 Year
Open (Enrolling)
Sarcoma, Soft Tissue Sarcoma, Bone Sarcoma

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Trial Information

A Phase I Trial of Dendritic Cell Vaccination With and Without Inhibition of Myeloid Derived Suppressor Cells by Gemcitabine Pre-Treatment For Children And Adults With Sarcoma

This is a dose finding / dose escalation study of dendritic cell (DC) vaccination
administered through imiquimod (Aldara®) treated skin for refractory sarcoma patients, which
includes a subsequent cohort of subjects who will receive DC and gemcitabine (Gemzar®)
therapy. There are three intended dose levels for cell number of DC per treatment - 3, 6 and
12 million cells per treatment. There will be 5 subjects accrued per dose level. If one
subject in the first 5 patients per dose level experiences a dose limiting toxicity (DLT),
then the dose level will be expanded to 8 subjects. If 2 or more of the subjects at a given
dose level experience a DLT, then the maximum tolerated dose (MTD) will be considered to
have been exceeded. The MTD will be the cell dose level at which less than 1 in 5 or less
than 2 in 8 subjects experience a DLT. Provision will be made to de-escalate to dose level
0, or 1.5 million cells per treatment, should dose level 1 be too toxic. This is a 5+3
design modified from the conventional 3+3 dose escalation schema used for testing cytotoxic
agents in Phase I trials. A lower rate of DLTs is therefore potentially to be accepted on
this study than on such a conventional dose escalation trial of a cytotoxic agent. If no MTD
is reached, we will consider the third dose level to be the recommended phase 2 dose (RP2D)
going forward and expand this dose level to 8 subjects in total.

After the MTD/RP2D is reached, we will commence with the addition of gemcitabine
pre-treatment to the study therapy with the cell dose held at the dose determined for the DC
alone. This will include weekly gemcitabine infusion for three weeks out of four before the
initiation of vaccination. Gemcitabine treatment will commence as soon as the subject has
safely recovered from pheresis, but within 2 weeks of completion of pheresis. DC vaccination
will begin two weeks after the third administration of gemcitabine. Gemcitabine dosing will
be constant, but should the combination of gemcitabine with the MTD/RP2D of DC alone prove
too toxic, we will de-escalate the dose of DC on the gemcitabine containing levels. This
de-escalation will mirror the dose escalation for DC alone, and the MTD for the DC plus
gemcitabine will be defined as the dose level at which less than 1 in 5 or less than 2 in 8
subjects experience a DLT.

At least two children, defined as subjects who were initially diagnosed with sarcoma before
the age of 21 years, must be included on each dose level to insure that the experience is
representative of the distribution of age levels found in sarcoma patients.

Subjects will undergo resection of tumor followed by pheresis to acquire monocytes which
will be separated and used to grow out DC. Subjects not undergoing gemcitabine therapy will
begin vaccination approximately two weeks after pheresis, depending on the manufacture time
of their DC. All subjects will undergo lysate boost administration.

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 study entry. 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. 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.

- 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) >750/L

- Lymphocytes > 500/L

- Platelets > 75,000/L

- Hemoglobin > 9 g/dL

- AST/ALT < 2.5 X ULN; if liver metastases, < 5 X ULN

- Serum Creatinine < 1.5 X ULN

- Total Bilirubin < 3 X ULN

- Albumin > 2 g/dL

- 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.

- Capable of understanding the investigational nature, potential risks and benefits of
the study and able to provide valid informed consent.

- 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 UM IRB

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

- Documented 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Outcome Description:

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.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

John Goldberg, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Miami Sylvester Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

July 2012

Completion Date:

July 2015

Related Keywords:

  • Sarcoma
  • Soft Tissue Sarcoma
  • Bone Sarcoma
  • Metastatic Sarcoma
  • Relapsed Sarcoma
  • Dendritic Cell
  • Myeloid Derived Suppressor Cells
  • MDSC
  • MDSC Inhibition
  • Osteosarcoma
  • Sarcoma



University of Miami Sylvester Comprehensive Cancer Center Miami, Florida  33136