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Gene thereapy of malignant gliomas: A phase 1 study of IL-4 and HSV-TK gene-modified autologous tumor to elicit an immune response
Age Group: Adults Only
Min Karnofsky Score: 60:
Requires occasional assistance but is able to care for most of own needs
Conditions:
Prior Surgery is Allowed
Prior Radiation is Allowed
Prior Chemotherapy is Allowed
Tumor Types:
Anaplastic Astrocytoma
Glioblastoma Multiforme
How does the experimental vaccine work? This research study involves the administration of an experimental vaccine, which contains your brain tumor cells that have been changed to make to make a hormone called interleukin-4 (IL-4). You will receive a series of vaccines in the thigh, where IL-4 is expected to help your own immune response fight against the brain tumor cells the same way human body`s immune response fights off infections, colds or flu viruses. The investigators hope this response will kill the cancer cells located in distant sites, such as the brain. The use of this vaccine is considered to be experimental and is not a FDA approved treatment for brain cancer. How is the experimental vaccine made? In order to make the experimental vaccine; samples of your brain tumor will be used. These samples would have been obtained previously by the surgeon at the time your tumor was removed to confirm the reappearance of your brain cancer. This procedure is not part of this study and you would have already signed a separate surgical consent. However, for the purposes of this study, you will need to have a section of skin about 2 inches by 4 inches in dimension removed from your abdomen. This will be used in the event the brain tumor cells collected do not make enough cells needed for the experimental vaccine. In the laboratory, the doctors will grow your brain tumor cells to make the vaccine. When enough brain tumor cells have been grown, a gene will be put inside each cell to cause them to make IL-4. Another gene used in the vaccine, called the herpes simplex virus-thymidine kinase (HSV-TK), makes a substance which is anticipated to kill the brain tumor cells used in the vaccine when a currently approved drug called Ganciclovir is given to you. Results from prior laboratory testing done by the investigators has shown that use of the HSV-TK gene in the vaccine with the subsequent administration of Ganciclovir may make giving the experimental vaccine safer to you. How will you receive this vaccine? On day 1, you will receive 5 injections of the experimental vaccine using a very small needle on the inner part of your upper thigh. The sites of these injections will be marked with permanent India ink to note their location for the doctor. Each site will contain different amounts of cells making different doses of IL-4. You will return to the clinic to see your doctor on days 1, 2, 4 and 7 after receiving these injections to evaluate any possible side effects. Each day, from days 8 to14, you will receive an anti-viral drug called Ganciclovir to help lessen the chance of the tumor growth at the site where you will be receiving the vaccinations on the thigh. This drug will be given through a vein in your arm, two times on each of these days. You will be watched carefully for any harmful side effects during or after receiving the drug. If there are none, then you will go home on the same day. On the 14th day, after receiving the experimental vaccines in your thigh, all 5 injection sites will be biopsied (a small amount of tissue will be removed), under local anesthesia, (a drug like novocaine will be used to numb the area so you will not feel pain). These biopsies or tissue samples will require 1 or 2 skin stitches to each site where the skin tissue is removed. The pieces of tissue from the injection sites on the thigh are being removed so that your doctor can see if the experimental vaccine is working. Chances are that if the biopsied tissue from the injection sites on your thigh does not show any response, that the vaccine may not be effective in killing the tumor cells in your brain. On day 15, you will be given 5 injections into the skin on your opposite thigh. In this vaccine, the doctors will use the largest amount of IL-4 that caused you the least amount of problems at the sites of your previous injections. Your doctor will be able to determine the amount of IL-4 to use based on whether you developed any problems at the site of the injections on the first thigh. Your doctor will be looking for skin problems such as redness, soreness, irritation or infection at the site where the injections were given. On days 16, 22 and 29 after re-administration of the vaccines on the opposite thigh, skin biopsies will be performed to evaluate the reaction to each vaccine. As before, these skin biopsies will be performed under local anesthesia, and will need 1 or 2 stitches. On each day, from days 22 to 28, 56 to 60 and 86 to 90, you will receive the drug Ganciclovir two times on these days. You will be watched carefully for any harmful side effects during and after receiving the Ganciclovir. If there are none, you will be will be able to go home on the same day. For follow-up evaluations, you will return to see your doctor every month for 3 months to evaluate your progress and response to this experimental treatment. During the course of this experimental treatment, blood will be drawn to measure the amount of lymphocytes. Lymphocytes are a type of white blood cell, which help you fight infections. The levels of IL-4 found in these lymphocytes will also be measured. There is a very small chance that tumor cells may grow at the vaccination sites on your thigh. Should this occur, the new tumor growths will be surgically removed. Do I have to pay for this experimental vaccine? Costs for participating in this experimental treatment, which are not part of the your standard of care for the treatment of your brain tumor, will be covered by a research grant. No research related costs would be billed to your insurance carrier. Examples of the research related procedures that are covered by the grant are as follows: · the costs for making the vaccine in the lab, · the administration of the vaccine, · the administration of the Ganciclovir and the drug itself, · the collection of blood samples for the measurement of the IL-4. Doctor`s visits, standard bloodwork, and MRI scans not associated with this research study, that would be done whether or not you participate in this study will be billed to your insurance. As always, a financial counselor is available to you to advise you on what is and is not covered by your insurance for standard care procedures.
Contact:
Ian F. Pollack MD, FACS
Walter Dandy Professor of Neurosurgery
Children`s Hospital of Pittsburgh
University of Pittsburgh School of Medicine
3471 Fifth Avenue
Pittsburgh, PA 15213 USA
Phone: 001 - 412 - 692-5881
Fax: 001 - 412 - 692-5921