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

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

Conditions

• AML/MDS
• B-ALL
• T-ALL
• BPDCN

Interventions

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

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Swati Naik, MD · St. Jude Children's Research Hospital

• Paulina Velasquez, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-07-29

Primary Completion

2029-07-29

Completion

2030-07-29

FDA Drug

Yes

Countries

• United States

Study Locations