Personalized immunotherapy clinical trials in practice
Personalized immunotherapy clinical trials in practice
Hands-on training is crucial
As the medical industry increasingly moves toward personalized medicine, there will be challenges for clinical trial sites that adapt to these types of studies.
Experts offer the example of the personalized immunotherapy studies underway for the treatment of cancer and HIV to show how it works.
Below is a nutshell look at personalized immunotherapy in three trials:
A closed-system centrifugation process separates red cells and part of the white blood cells from the monocytes, leaving behind a monocyte-enriched cell preparation, while the other blood ingredients are recirculated into the patient's circulatory system, explains Lothar Finke, MD, chief medical officer and vice president, regulatory affairs, for Argos Therapeutics of Durham, NC, which is sponsoring three CTs involving a personalized immunotherapy approach.
Trial participants stay on a leukapheresis machine for nearly four hours while their white blood cells are collected for retrieval of dendritic cells. Patients are monitored in a hospital setting, Sékaly says.
So far, the three trials, including the latest one with HIV patients, have not had any unanticipated problems, says Rafick-Pierre Sékaly, PhD, a professor in the department of microbiology and immunology and a Canada research chair in human immunology at the Université de Montréal in Quebec, Canada. Sékaly is studying the personalized immunotherapy approach in HIV patients.
Once the white blood cells are collected, they are carefully labeled and sent to Argos' laboratory in Durham, where they are prepared as a presentation platform for the generation of the patient's individualized anti-viral therapy, which is ultimately filled into vials, frozen, and shipped one by one for every single treatment visit, to the sites, Finke says.
"The fresh cells have to be shipped to us in a very controlled process because these cells are alive, and need to stay alive, and then we culture them into dendritic cells," Finke says.
"We use RNA from the virus or the tumor, which has been amplified previously, so that we can basically take a small sample of RNA virus and make lots of RNA identical to the patient's original material," Finke explains. "Then we put the two together by a process called electroporation, which applies an electric current that gets the RNA into it."
The antigens are expressed under dendritic cells, processed, and then the dendritic cells present these virus- and tumor-specific antigens to the patient's immune system, Finke says.
Further lab work results in a cryopreserved vial that is shipped back to the clinical trial site, one at a time, where it is injected into the patient's skin, Finke adds.
The hopes are that the process will encourage the patient's T-cells to generate memory of the virus or tumor and create more T-cells that can attack the diseased cells, in effect boosting the patient's immune system with his or her own recharged dendritic blood cells, Finke says.
1. The sponsor is cautious when selecting CR sites.
"We are concentrating on sites and physicians who are advocates of, and versed in, immuno-therapy," Finke says. "Usually these people have a background in immunotherapy or immunology of cancer and are much more familiar with the procedures that we require than the usual oncologist or urologic surgeon.
Another important prerequisite is that the site has a leukapheresis unit, Finke notes.
"We need to have sites that have good access to that resource," he says.
Sites need to be able to follow relatively strict scheduling and logistics systems to align with manufacturing and treatment shipments, Finke adds.
The first trial included a site that didn't have a leukapheresis unit, so CR staff used a unit at a Red Cross site about 35 minutes away, says Jeffrey Abbey, MBA, JD, vice president of business development for Argos Therapeutics.
This site is no longer a part of the research, and all current sites have their own units, Abbey adds.
2. Site training is hands-on and extensive.
In the planning process of the protocol, clinical sites are usually involved in generating details of the protocols, Finke notes.
Once the trials are underway, all sites, and especially new sites unfamiliar with the processes, are visited by an entire team to provide the necessary training.
The training meeting covers the shipment logistics and other information, including these details:
- How do you get the drug?
- What does the container look like?
- How do you unpack the container?
- How is the product injected?
- How does one pack a tumor specimen?
- Where do the Gel packs go?
- Where is the temperature recorder?
- How do you order a pick-up and delivery for Argos?
This training session will take an entire day and include a dry run of the process, and it's required that everyone involved in any part of the clinical trial attend the meeting, Finke says.
The hands-on training has staff use all of the very same materials they would use during the clinical trial. For instance, there are gel packs, temperature recorders, etc.
While the typical investigator meeting might be attended by the principal investigator and one or two other people from the CR site, these meetings must be attended by everyone who touches any component of the research, Finke says.
"Sometimes site training takes additional attention, and we have to go through the process again" Finke notes. "But people are enthusiastic and very dedicated, so the training is falling on fertile ground."
Any CR investigator or coordinator who has questions during the trial will be able to reach someone who can help them, he says.
"We've shipped almost 200 samples now, and with one exception, we haven't had any systematic problems," Finke says.
3. Extra attention is paid to identifying and matching material.
"We put a unique identifier system in place that consists of a drug designator, site, and patient number, and samples are made completely anonymous," Finke says. "There are a lot of structures in place to make sure there is no mixing of samples, and that's something the FDA is very concerned about."
Each time there's a change in the trial, it's discussed with the FDA, he adds.
The material sometimes is identified through bar codes, and sometimes there are two people in place to make sure that one compares the number on the vial with the paperwork, which is checked by the other person, Finke explains.
As the medical industry increasingly moves toward personalized medicine, there will be challenges for clinical trial sites that adapt to these types of studies.Subscribe Now for Access
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