A Phase I Trial of Surgical Resection Followed by Vaccination With Dendritic Cells Pulsed With Tumor Lysate With Imiquimod for Patients With Malignant Glioma
Dendritic cells are a small group of cells contained in everyone's white blood cell
population. These cells are responsible for letting the immune system know that something
foreign is in the body. Dendritic cells help the body ward off disease by alerting the
Imiquimod in an FDA-approved cream that is an immune response modifier, which will be used
off-label in this study. Imiquimod cream (5%, 250 mg) will be self-applied topically by
patients to a 4 x 5-cm outlined area of healthy skin overnight on days 1-5 of each cycle.
Application and removal times will be recorded in treatment diaries. Dendritic cells will be
injected intradermally into the imiquimod-treated site on day 3. Cycles will be repeated
every 2 weeks for a total of three injections. This study will examine the effectiveness of
using Imiquimod with DC vaccines, as previous studies within the oncology department have
studied the effectiveness of DC vaccines.
Imiquimod (Aldara, 3M) is one of the better characterized imidazoquinolines and is the only
one currently approved for clinical use as a topical ointment. It has been demonstrated to
possess antiviral and antitumor properties, and it is approved for the treatment of genital
warts. Vaccination studies in animal models have indicated that imidazoquinolines can boost
the magnitude and quality of T cell responses. It is considered a Toll-like receptor agonist
which controls the activation of dendritic cells.
In humans, it was shown that topical imiquimod treatment may enhance the immunogenicity of a
melanoma vaccine. Additionally, injection of immature DCs into imiquimod-pretreated skin
lead to DC activation in situ and enhanced migratory capacity to draining lymph nodes in
cancer patients. In this study, the investigators test the safety and feasibility of
imiquimod in a vaccine against brain cancer to induce a more potent immune response that
what has previously been observed.
In prior Phase I and Phase II studies, patients who received chemotherapy following DC
demonstrated longer progression free and overall survival than the patients who received DC
or chemotherapy alone. The use of DC vaccines is considered investigational and has not yet
been approved by the FDA, but the investigators have obtained an IND for use of the
The purpose of this study is to determine whether after standard therapy of tumor resection
surgery followed by DC vaccines with Imiquimod will not only generate (start) an immune
response, but will provide longer progression-free survival. Subjects will have clinically
indicated resection surgery and will consent to our screening study for vaccine trials (IRB
#9225), under which subjects will have their tumor tissue analyzed in order to verify
eligibility into this study.
Study procedures include the following: laboratory blood draws, urinalysis at screening,
immunological testing, administration of the quality of life questionnaire, neurological
exams, MRI testing, leukapheresis for dendritic cells, review of adverse events/concomitant
Patients who were screened and not enrolled in this clinical trial due to screen failure
will be notified of the reason for screen failure. Pre HIV counseling and appropriate
referral resources will be provided. If the screen failure is due to the positive HIV test,
appropriate post HIV counseling will be provided and appropriate referrals will be made. The
charts of the patients with screen failures will be destroyed. The patients' charts who will
be enrolled in the study will be kept in the locked cabinet in the research office. Patients
will be assigned a unique identifying code known only to the research team. Data will be
captured by various source documents, or, as necessary, abstracted from hospital medical
records by an experienced registered nurse. The electronic data for viral testing will be
accessible to research personnel only.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
safety of an autologous tumor lysate- loaded dendritic cell (DC) vaccine with Imiquimod cream application
Safety relative to vaccine will be monitored in terms of Serious Adverse Events according to FDA regulations and recorded on a MedWatch 3500a form. A Data Safety Monitoring Committee will meet every 6 months to review AEs/SAE's. In the event of any subject death within a 30 day period following study agent administration, the DSMC will review the death within that time frame. If two deaths are deemed to be "probably" or "definitely' related to study agent administration, all study agent administrations will be stopped and the FDA and IRB will be notified of study cessation.
John Yu, MD
Cedars-Sinai Medical Center
United States: Food and Drug Administration
|Cedars Sinai Medical Center||Los Angeles, California 90048-1804|