Last updated on December 2018

Dendritic Cell Vaccine With or Without Gemcitabine Pre-Treatment for Adults and Children With Sarcoma


Brief description of study

The use of adjuvant vaccination with autologous dendritic cells (DC) matured in situ after being loaded with tumor lysates derived from autologous refractory sarcoma tissue will be safe, feasible and potentially beneficial for patients diagnosed with sarcoma. This vaccination will result in evidence of immune stimulation against tumor antigens. In addition, combining myeloid derived supressor cells (MDSC) inhibition using gemcitabine with DC vaccination in this method will be safe and feasible and show improved immune parameters over DC vaccination without MDSC inhibition.

Detailed Study Description

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.

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.

Clinical Study Identifier: NCT01803152

Contact Investigators or Research Sites near you

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Breelyn Wilky, MD

University of Miami
Miami, FL United States
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Recruitment Status: Open


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