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Dr. Sallman, AML expert from Moffitt Cancer Center in Tampa, Florida discusses with us his phase 1/1b safety study of PRGN-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia.
Dr. Sallman states that this study is a first in human CAR-T study including patients with relapsed or refractory AML or MDS. CAR-T development for AML is early but has shown great success in other blood cancers such as multiple myeloma, acute lymphoblastic leukemia (ALL) and lymphoma so researchers are hoping to be able to say the same about its use in AML in the near future.
According to the National Cancer Institute, CAR-T therapy is a type of treatment in which a patient’s T-cells (a type of immune cell) are changed in the laboratory so they will bind to cancer cells and kill them. Blood from a vein in the patient’s arm flows through a tube to an apheresis machine, which removes the white blood cells, including the T cells, and sends the rest of the blood back to the patient. Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR-T cells are grown in the laboratory and then given to the patient by infusion. The CAR-T cells are able to bind to an antigen on the cancer cells and kill them.
One of the two main targets for CAR-T in AML is CD33 which is an antigen that is found on the surface of AML blasts. CD33 is the target of the CAR in Dr. Sallman’s study. Other unique features of the PRGN-3006 Ultracar-T include its membrane-bound IL-15 which allows the CAR-T to grow in the patient. It also contains a kill switch, so if there is significant toxicity to the patient and doctors need to eliminate the CAR immediately, it can be turned off. The manufacturing of this CAR-T is quite unique in that it is not the traditional viral-vector system which can take up to 3-4 weeks to make. This CAR-T utilizes a sleeping beauty plasmid which makes apheresis to infusion a two day process with overnight manufacturing. This whole process can occur directly at the academic center where the patient is being treated. With this system, the patient can be treated at the right time and rapidly.
Study Results
This study contains 2 cohorts, a lymphodepletion group and a non-lymphodepletion group. The process of lymphodepletion consists of the patient receiving chemotherapy days before the CAR-T cells are infused. This chemotherapy aims to decrease the number of T cells in the body in order to make room for new CAR-T cells.
Three out of six patients had an objective response after the first two dose levels in the lymphodepletion group. One patient was able to make it to stem cell transplant and has been in remission for over a year, and two other remissions were seen in heavily relapsed/refractory patients that lasted for about 3 months.
Dr. Sallman reports they are seeing great kinetics of this CAR-T with nice peak expansion occurring around day 14. Tolerability is good with grade 1-2 cytokine release storm in most cases, and they are seeing bone marrow infiltration.
This trial is ongoing. You can learn more about the trial by visiting our
Dr. Sallman, AML expert from Moffitt Cancer Center in Tampa, Florida discusses with us his phase 1/1b safety study of PRGN-3006 Ultracar-T in Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia.
Dr. Sallman states that this study is a first in human CAR-T study including patients with relapsed or refractory AML or MDS. CAR-T development for AML is early but has shown great success in other blood cancers such as multiple myeloma, acute lymphoblastic leukemia (ALL) and lymphoma so researchers are hoping to be able to say the same about its use in AML in the near future.
According to the National Cancer Institute, CAR-T therapy is a type of treatment in which a patient’s T-cells (a type of immune cell) are changed in the laboratory so they will bind to cancer cells and kill them. Blood from a vein in the patient’s arm flows through a tube to an apheresis machine, which removes the white blood cells, including the T cells, and sends the rest of the blood back to the patient. Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR-T cells are grown in the laboratory and then given to the patient by infusion. The CAR-T cells are able to bind to an antigen on the cancer cells and kill them.
One of the two main targets for CAR-T in AML is CD33 which is an antigen that is found on the surface of AML blasts. CD33 is the target of the CAR in Dr. Sallman’s study. Other unique features of the PRGN-3006 Ultracar-T include its membrane-bound IL-15 which allows the CAR-T to grow in the patient. It also contains a kill switch, so if there is significant toxicity to the patient and doctors need to eliminate the CAR immediately, it can be turned off. The manufacturing of this CAR-T is quite unique in that it is not the traditional viral-vector system which can take up to 3-4 weeks to make. This CAR-T utilizes a sleeping beauty plasmid which makes apheresis to infusion a two day process with overnight manufacturing. This whole process can occur directly at the academic center where the patient is being treated. With this system, the patient can be treated at the right time and rapidly.
Study Results
This study contains 2 cohorts, a lymphodepletion group and a non-lymphodepletion group. The process of lymphodepletion consists of the patient receiving chemotherapy days before the CAR-T cells are infused. This chemotherapy aims to decrease the number of T cells in the body in order to make room for new CAR-T cells.
Three out of six patients had an objective response after the first two dose levels in the lymphodepletion group. One patient was able to make it to stem cell transplant and has been in remission for over a year, and two other remissions were seen in heavily relapsed/refractory patients that lasted for about 3 months.
Dr. Sallman reports they are seeing great kinetics of this CAR-T with nice peak expansion occurring around day 14. Tolerability is good with grade 1-2 cytokine release storm in most cases, and they are seeing bone marrow infiltration.
This trial is ongoing. You can learn more about the trial by visiting our
about the author
Katie Braswell
Katie joined HealthTree as the Community Director for AML in 2021. She is a registered dietitian who previously worked at the VA hospital in Dallas, Texas where she coached veterans with blood cancer on how to use nutrition to improve their treatment outcomes and minimize cancer-related side effects. Katie is passionate about health education and patient empowerment. In her spare time, she loves to experiment with new recipes in the kitchen, spend time running outdoors and travel to new places.
