Oncologists at Riley Children’s Health, in collaboration with basic science researchers in the Brown Center for Immunotherapy at Indiana University School of Medicine, are leading two Phase I CAR-T cell clinical trials for acute myeloid leukemia (AML) and T-cell acute lymphocytic leukemia (ALL). Both trials target CD4. In research seeking to minimize toxicity of intensive cancer therapy, Riley Children’s is also participating in a high-profile, multicenter National Cancer Institute (NCI) trial investigating the elimination of total body irradiation (TBI) before stem cell transplant for certain B-ALL patients.
CD4 CAR-T Cell Therapy for AML
Phase I study for children and adults – enrolling 20 patients
The study uses autologous CD4 CAR-T cells that are engineered to express a chimeric antigen receptor (CAR) targeting CD4 that is linked to the cluster of differentiation 28 (CD28), 4-1BB, cluster of differentiation 3-zeta (CD3ζ) signaling chains (third generation CAR). About 70% of AML with monocytic differentiation and 37% of all other AML express CD4 on their blasts.
CD4 CAR-T Cell Therapy for T-cell ALL
Phase I multicenter study for children and adults – enrolling up to 30 patients
The study uses autologous T-cells transduced with a lentiviral vector to express the scFv nucleotide sequence of the anti-CD4 molecule. The protocol is for patients with unmet medical needs for which there are no current effective therapies.
View active hematology and oncology clinical trials at Riley Children’s.
“The Brown Center for Immunotherapy, which is comprised of 80% bench scientists in cellular therapy, opens up numerous possibilities for IU-led CAR-T clinical trials for both children and adults at Riley Children’s and IU Health,” said Jodi Skiles, MD, director of pediatric stem cell transplant and cellular therapy at Riley Children’s. “There are currently three open first-in-human CAR-T trials that originated in the Brown Center, based on previously demonstrated success in animal models for T-ALL, AML, and CMML.”
An additional strength of the clinical trial program at Riley Children’s is IU School of Medicine’s viral vector lab. Highly regarded in the gene therapy community nationally, the Indiana University Vector Production Facility has generated more than 120 clinical gene therapy and vector products for Phase I and Phase II trials since 1995.
NCI EndRAD trial aims to minimize toxicity
Riley Children’s is also participating in EndRAD, an NCI trial that stratifies B-ALL patients with a low risk of relapse using NGS-MRD (next generation sequencing-minimal residual disease). Specifically, the study is evaluating the elimination of radiation from the preparative regimen for patients with ALL who are undergoing hematopoietic cell transplant.
“This study is critically important because radiation (which is the current standard of care preparative regimen for children with ALL) is one of the most toxic forms of therapy. While it is very effective at eradicating leukemia cells, it is particularly problematic in children who still have developing brains and are at high risk for neuro-cognitive side effects,” Dr. Skiles said.
In addition, Riley Children’s recently conducted its first two transplants utilizing alpha/beta T-cell depletion cellular manipulation, which helps to minimize toxicity of transplant and reducing non-relapse mortality. Also within the Hematology, Oncology and Stem Cell Transplant program, Riley experts are leading cellular therapy treatments, including infusions of viral specific T cells and NK cells.
Riley Children’s, an experienced clinical trial partner with the NCI, the Children’s Oncology Group, the Early Phase Network and 10 other major research organizations, is well-known nationally for excellence in clinical trial coordination. The pediatric health system has an established, proven process for expedient Institutional Review Board (IRB) and Scientific Review Committee (SRC) approval and is supported by a team of research specialists and research coordinators with years of experience in clinical research.