About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≤21 years old
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
Relapsed disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies including
Disqualifiers
Known primary immunodeficiency
History of HIV infection
Severe intercurrent uncontrolled bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection)
History of hypersensitivity reactions to murine protein-containing products
Trial design
Single group
Treatments tested in this trial
CD123-CAR T
DrugTo treat relapsed/refractory CD123+ AML/MDS, B-ALL, T-ALL or BPDCN patient population that needs new cancer-directed therapies.
Cyclophosphamide
DrugCyclophosphamide 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.
Fludarabine
DrugFludarabine 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
Mesna
DrugMesna 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
Rituximab
DrugRituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes
Treatment groups
Trial outcomes
Primary outcomes
Maximum tolerated dose of CD123-CAR T cells (CATCHAML)
A phase I design to determine the maximum tolerated dose (MTD) of autologous, CD123- CAR T cells. Four dose levels (3x10\^5/kg, 1x10\^6/kg, 3x10\^6/kg, and 1x10\^7/kg) will be evaluated.
Sponsors and contacts
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