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A PHASE IIb CLINICAL TRIAL OF AN INVESTIGATIONAL VACCINE (CT-107) FOR THE TREATMENT OF NEWLY DIAGNOSED GBM FOLLOWING RESECTION AND CHEMO-RADIATION (IRB #24396)
This randomized, double-blind, multi-center, controlled study is designed to evaluate the use of a vaccine for people that have been newly diagnosed with a specific brain tumor (glioblastoma multiforme, or GBM) and have had surgery to remove the tumor. The vaccine (ICT-107) is made from the patients own blood cells, and may act as a “vaccination” against the tumor to keep it from coming back so soon. This vaccine has not yet been approved by the U.S. Food and Drug Administration (FDA).
This study consists of a 6-week Post Surgery Standard of Care Treatment Phase; 6-week Vaccine Induction Phase; a 1 week rest period; and a Maintenance Phase consisting of 28-day cycles. Standard of Care (SOC) chemoradiation (radiotherapy and temozolomide [TMZ]) will be administered during the Post Surgery Standard of Care Treatment Phase; SOC maintenance TMZ will be administered for 12 cycles (12 months) during Maintenance.
Participants will be patients who have had clinically indicated surgery to remove their brain tumor. These patients will be screened for eligibility, and if eligible, will undergo a procedure called apheresis through which the individual's study vaccine will be made.
Apheresis involves the subject giving components of their blood to make the vaccine and then the vaccine made from that blood will be given back to them as the study medication. During this procedure, blood will be drawn from the subject's vein, circulated through a machine which will collect the mononuclear cells from the blood, and then the remainder of the blood cells are returned to the subject's body. This procedure pumps blood through a machine to collect specific cells from the blood, and the remainder of the blood cells are returned back to the subject's body. The blood cells that are collected will be divided. Some of the blood cells will be treated so that they will recognize the tumor cells produced by the patients tumor; this will be the ICT-107 vaccine. The rest of the cells will not be treated; this will be the Control vaccine. The Control vaccine will not have any effect on the tumor. ICT-107 is an autologous vaccine consisting of the patient’s DCs pulsed with synthetic peptides from 6 tumor-stem cell associated antigens; matching Control consists of unpulsed DCs at one third the number of cells.
The study vaccine a subject gets will be specific for them. There will be very strict procedures put in place to make sure a subject doesn't get a vaccine made from someone else’s blood. Vaccines are tracked throughout the course of the study via appropriate sample labeling, identifier codes and cross verification at the production facility (University of Pennsylvania) and study site. After the subject's blood cells have been collected, subjects will begin radiation and chemotherapy treatment (standard of care).
After the chemotherapy is completed, the doctor will assess whether the subject is still eligible to be in the study. Subjects who continue to be eligible will be randomized to treatment by site and age, Regardless of whether a subject receives ICT-107 or Control, they will also get the regular radiation therapy and chemotherapy(standard of care).
Subjects will receive the same study vaccine throughout the study, and the investigator nor the subject will know which vaccine the subject is receiving.
Schedule for Vaccine Administration: During the Vaccine Induction Phase, the study vaccine will be given once a week for three weeks, after which there will be a 1-week rest period. Next, maintenance doses of TMZ will be administered at 5 days a month for 12 months (Day 1 to Day 5 during Cycles 1 to 12). During this time, subjects will have study visits on Weeks 1 and 3. Maintenance vaccines will be administered on Day 21 (Week 3) of Cycles 1, 3, 6 and 10. If administration of Maintenance TMZ is delayed at any time, maintenance vaccination will also be delayed accordingly, to ensure that administration of Maintenance TMZ and Maintenance Vaccine remains synchronized. For Cycles 13 beyond, subjects will have study visits on Week 3 of every cycle, and extended Maintenance Vaccines only from Cycles 16, 22 and continuing every 6 months until depletion of study treatment or confirmation of Progressive Disease, whichever comes first.
If at any time the results of the Tumor Assessment Visit make the study doctor think the tumor has come back, patients will have to return to CSMC in about 4 weeks to have the tumor assessment procedures done again. During these 4 weeks they will continue to take any medication (temozolomide or study vaccine) if scheduled to do so. If the study doctor confirms that the tumor has NOT come back, patients will continue in the study and continue the regular schedule of study visits. If the doctor confirms that the tumor HAS come back patients will not receive any more study medication. The study doctor will discuss the various options with them and they will also have the End of Study Visit assessments done. After the End of Study Visit, the study doctor will call patients about once every 3 months for survival status.
Per protocol, University of Pennsylvania will prepare both the active vaccine and Control for each subject from his/her de-identified apheresis product. Also, subject's de-identified blood sample from screening will be forwarded to the University of California, San Francisco, where analysis will be performed to confirm that the patient has HLA-1 or HLA-2 status needed to meet entry criteria.
Pregnant women and children will not be eligible to receive the study intervention. Involvement of pregnant women will be limited to the adverse event in which a female subject (or female partner of a male subject) becomes pregnant during the course study. If a woman becomes pregnant during the course of the research, information regarding the pregnancy as well as information regarding the outcome of her pregnancy will be monitored for research purposes. As the monitoring will be limited to obtaining data related to the course of the pregnancy and birth outcomes, there are no physical risks for pregnant woman and the newborns whose medical records may be reviewed. The collection of such information poses no greater than minimal risk for these populations and is described in the consent form. Consent/parental permission to review the medical records will be obtained from the pregnant women via the study consent form.
Surasak Phuphanich, MD, FAAN
Director, Neuro-oncology Program