NCT04318678

CD123-Directed T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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

Detailed 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 Collection and Manufacturing Phase; chemotherapy is given for several days prior to the cellular infusion. You are then monitored for any possible side effects. . Chemotherapy is given to get your body ready to accept the CATCHAML treatment. Treatment Schedule: Patients will receive lymphodepleting chemotherapy followed by infusion of CD123-CAR T cells Fludarabine on day -4, -3 and -2 Cyclophosphamide on day -3 and -2 REST DAY on day -1 CD123-CAR T cell infusion on day 0 or +1

Conditions

• AML/MDS
• B-ALL
• T-ALL
• BPDCN

Interventions

Type	Name	Description
DRUG	CD123-CAR T	To treat relapsed/refractory CD123+ AML/MDS, B-ALL, T-ALL or BPDCN patient population that needs new cancer-directed therapies.
DRUG	Cyclophosphamide	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.
DRUG	Fludarabine	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
DRUG	Mesna	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
DRUG	Rituximab	Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes

Timeline

• Start date: 2020-07-29
• Primary completion: 2029-07-29
• Completion: 2030-07-29
• First posted: 2020-03-24
• Last updated: 2026-03-30

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study