This phase I trial tests the safety, side effects, and best dose of CART-45 cells, given after CD45 base-edited hematopoietic and progenitor stem cell (CD45BE-HSPC) transplant, for the treatment of lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). A stem cell transplant is a type of treatment for patients with blood cancers such as lymphoma and is often referred to as a bone marrow transplant. However, the stem cells (or bone marrow cells) given as part of this study will be modified in a laboratory. This modification is a genetic change to normal cells. A protein called CD45 is normally expressed on stem cells. The genetic change performed in the laboratory modifies how these CD45 proteins appear in the body, without changing how these proteins work. This makes the healthy stem cells “invisible” to the CART-45 cells administered after the stem cell transplant. This protects the CD45 proteins from this targeted therapy. Chimeric antigen receptor T cells are a type of immunotherapy drug. In order to make the CART-45 cells, some of a patient's white blood cells, called T cells, are collected. These cells are then modified in a laboratory to recognize and target a protein on the surface of the cancer cells called CD45. This modification is a genetic change, or gene transfer, to the normal T cells. The CART-45 cells will be administered about 35 days after you undergo the CD45BE-HSPC transplant. This allows for the healthy cells to be protected from the CART-45 cells, while still letting the CART-45 cells recognize and attack cancer cells. Prior to the CD45BE-HSPC transplant and CART-45 infusion, conditioning regimens with carmustine, etoposide, cytarabine, melphalan, and other chemotherapy drugs may be administered in order to prepare the body for transplant. Administering CART-45 cells following a CD45BE-HSPC transplant may be a safe and feasible treatment option for patients with relapsed or refractory lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07451054.
Locations matching your search criteria
United States
Pennsylvania
Philadelphia
University of Pennsylvania/Abramson Cancer CenterStatus: Active
Contact: Noelle Frey
Phone: 215-662-2867
PRIMARY OBJECTIVES:
I. Evaluate the safety of an autologous transplant of autologous CD45 base-edited HSPCs (CD45 base edited hematopoietic stem and progenitor cells [CD45BE-HSPC]).
II. Evaluate the safety of autologous base-edited anti-CD45 CAR-T cells (CART-45) cells administered post-CD45BE-HSPC transplant.
SECONDARY OBJECTIVES:
I. Evaluate manufacturing feasibility.
II. Evaluate study feasibility.
III. Describe preliminary efficacy.
EXPLORATORY OBJECTIVES:
I. Persistence of engrafted CD45BE-HSPCs.
II. Persistence and trafficking of CART-45 cells.
III. CART-45 bioactivity.
OUTLINE: This is a dose-escalation study of CART-45 cells in combination with CD45BE-HSPCs.
Patients undergo apheresis twice for the manufacturing of the CD45BE-HSPCs and CART-45 cells on study.
PRE-TRANSPLANT CONDITIONING: Patients receive carmustine intravenously (IV) on day -7, etoposide IV on days -6 to -3, cytarabine IV twice daily (BID) on days -6 to -3, and melphalan IV on day -2.
CD45BE-HSPC TRANSPLANT: Patients receive CD45BE-HSPCs IV on day 0, at least 24 hours following the last dose of pre-transplant conditioning.
LYMPHODEPLETION: Patients receive lymphodepleting chemotherapy at the physician's discretion, with the last dose completed 2-5 days prior to CART-45 infusion (day 35).
CART-45 TRANSPLANT: Patients receive CART-45 cells IV on day 35.
RE-TREATMENT: Patients who demonstrate clinical benefit from initial CART-45 cell infusion may optionally receive retreatment with CART-45 cells, with or without lymphodepletion, at the discretion of the physician.
IMAGING AND INVASIVE PROCEDURES: Patients undergo echocardiography (ECHO)/multigated acquisition scan (MUGA) at screening and undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT, bone marrow biopsy (BMB)/bone marrow aspiration (BMA), and collection of blood samples throughout the trial. Patients may undergo biopsy at screening and on study.
After completion of study treatment, patients are followed up on days 1, 4, 7, 10, 14, 21, and 28 following CART-45 cell infusion, and in months 3-6, 9, and 12, and then up to 15 years following CD45BE-HSPC transplant.
Lead OrganizationUniversity of Pennsylvania/Abramson Cancer Center
Principal InvestigatorNoelle Frey
