The study is designed to examine the feasibility and safety of collecting autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy for patients with relapsed/refractory (r/r) hematological disease. The study will evaluate feasibility of collecting the target dose of HSCs from at least 50% of enrolled patients. The study will assess safety based on incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the first 60 days post CAR T dosing, and also through the collection of adverse events (AEs) and serious adverse events (SAEs) as well as the durability of response after treatment with HSCs with CAR T. The study follows an open-label, single-center and single non-randomized cohort design. 20 subjects with r/r hematological malignancies will be enrolled and treated to evaluate the feasibility and preliminary safety of collecting autologous HSCs and combining them with CAR T-cell therapy.
Age 18 - 85 years.
Histologically proven hematological malignancy according to the World Health Organization 2016 classification criteria for which a commercially available, FDA-approved CAR T product exists.
Disease progression after last regimen, or
Refractory disease: failure to achieve a partial response (PR) or complete remission (CR) to the last regimen
Autologous hematopoietic cell transplant intent or execution within 8 weeks of planned CAR T infusion.
History of allogeneic cell transplantation within 8 weeks of planned CAR T infusion.
Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management at time of screening.
History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
Single group
autologous hematopoietic stem cells added to planned CAR T
Biological/VaccineAutologous hematopoietic stem cells (aHSCs) infused on Day 10 after CAR T (any FDA-approved CAR T product) infusion on Day 0.
To assess feasibility of collecting the target HSC cell dose for at least 50% of enrolled patients.
Target dose collection of autologous HSCs (2 to 5 x 106 CD34+ cells/kg) defined as collection from at least 50% of patients enrolled in this study by Day 10.
To assess safety of aHSC to planned CAR T therapy in the first 60 days through the incidence, severity, and duration of CRS based on the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system.
Safety will be assessed by incidence, severity, and duration of CRS per ASTCT consensus grading system. ASTCT CRS Consensus grading (Grade scale is 1-4) is based on 3 CRS parameters: fever, hypotension, and hypoxia. Higher grade indicates worse outcome.
To assess safety of aHSC to planned CAR T therapy in the first 60 days through the incidence, severity, and duration of ICANS based on the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading system.
Safety will be assessed by incidence, severity, and duration ICANS per ASTCT consensus grading system. ASTCT ICANS Consensus grading (Grade scale is 1-4) is based on 5 neurotoxicity domains: Immune Effector Cell-Associated Encephalopathy (ICE) score, level of consciousness, seizure, motor findings, raised intracranial pressure (ICP)/cerebral edema. Higher grade indicates worse outcome.
Response rate of CAR T at 6 weeks.
Response rate of CAR T will be defined as the proportion of subjects who experience partial response (PR) or complete response (CR) assessed at 6 weeks or day 60. Response criteria used will be according to type of disease: Response by International Myeloma Working Group (IMWG) Criteria (for multiple myeloma); Response by Center for International Blood and Marrow Transplant Research (CIMBTR) Criteria (for acute lymphoblastic leukemia); Response by Lugano Criterial (for lymphoma).
Assess rate of recovery of absolute neutrophil count (ANC) by Day 28.
Recovery assessed by the proportion of patients with ANC recover to ≥ 500/µL.
Assess red blood cell (RBC) count and transfusion independence by Day 28.
The proportion of patients with RBC transfusion independence by Day 28.
Assess platelet count and transfusion independence rate by Day 28.
The proportion of patients with platelet transfusion independence by Day 28.
Click on the lead sponsor to view all of their trials.
Joshua Sasine, MD, PhD
Lead sponsor
Cedars-Sinai Medical Center
Sponsor institution
