CD123-Directed T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
St. Jude Children's Research Hospital
Summary
The CD123-CAR T-cell therapy is a new treatment that is being investigated for treatment of AML/myelodysplastic syndrome (MDS), T- or B- acute lymphoblastic leukemia (ALL) or blastic plasmacytoid dendritic cell neoplasia (BPDCN). The purpose of this study is to find the maximum (highest) dose of CD123-CAR T cells that is safe to give to these patients. This would include studying the side effects of the chemotherapy, as well as the CD123-CAR T-cell product on the recipient's body, disease and overall survival. Primary Objective: * To determine the safety of one intravenous infusion of escalating doses of autologous, CD123-CAR T cells in patients (≤21 years) with recurrent/refractory CD123+ disease (AML/MDS, B-ALL, T-ALL or BPDCN) after lymphodepleting chemotherapy. * To determine the safety of an intravenous infusion of escalating doses of donor derived, CD123-CAR T cells in patients (≤21 years) with recurrent/refractory CD123+ disease (AML/MDS, B-ALL, T-ALL, BPDCN or MPAL) after lymphodepleting chemotherapy. Secondary Objectives \- To evaluate the antileukemia activity of CD123-CAR T cells. Exploratory Objectives * To assess the immunophenotype, clonal structure and endogenous repertoire of CD123-CAR T cells and unmodified T cells * To characterize the cytokine profile in the peripheral blood and CSF after treatment with CD123-CAR T cells * To characterize tumor cells post CD123-CAR T-cell therapy * To compare in vivo properties of donor-derived versus autologous CD123- CAR T cells
Description
This study will evaluate the safety and maximum tolerated dose of CD123-CAR T cells. This study contains 2 phases. The first part is the called the "Collection and Manufacturing Phase" and the second is the "Treatment Phase". The Collection and Manufacturing Phase refers to your blood cells being collected and possibly frozen, via a process called apheresis. These cells will then be changed to improve their ability to recognize and kill cancer cells. The Treatment Phase refers to the portion of the study in which you receive an infusion of the CD123-CAR T cells that were made in the Collect…
Eligibility
- Age range
- Up to 21 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria for Procurement and T-cell Production: * Age ≤21 years old * Relapsed/refractory CD123+ disease defined as follows: AML/MDS * Relapsed disease: Patients developing recurrent disease after a first complete remission (CR) * Refractory disease: Patients not achieving a CR after 2 cycles of induction chemotherapy B-cell ALL * Relapsed disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies including * Patients in 2nd or greater relapse * Patients with relapse after allogeneic HSCT * Refractory disease that is CD…
Interventions
- DrugCD123-CAR T
To treat relapsed/refractory CD123+ AML/MDS, B-ALL, T-ALL or BPDCN patient population that needs new cancer-directed therapies.
- DrugCyclophosphamide
Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA.
- DrugFludarabine
Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis
- DrugMesna
Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide
- DrugRituximab
Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes
Locations (2)
- St Jude Children's Research HospitalMemphis, Tennessee
- St. Jude Children's Research HospitalMemphis, Tennessee