This is a phase 1 clinical trial evaluating the use of autologous T cells, genetically engineered to express CD123-specifc chimeric antigen receptors (CD123-CARs), in pediatric and young adult patients with relapsed/refractory CD123+ acute myelogenous leukemia (AML). We will also include a subset of patients with B-cell acute lymphoblastic leukemia (B-ALL) T-cell ALL or blastic plasmacytoid dendritic cell neoplasm (BPDCN) who are CD123+ after lymphodepleting chemotherapy.
CD123 is an AML-associated antigen that is a viable tumor target because of its predictable expression on leukemic blasts, with enrichment in the cancer stem cell population. Preclinical data generated by our group and other investigators have shown promising results in AML treatment with engineered immune effectors directed to the CD123 antigen.
This clinical trial uses a lentiviral vector encoding a second-generation CD123-specific CAR and a CD20 safety switch. This vector is produced in the St. Jude Good Manufacturing Practices facility using a transient producer cell line.
Therapy includes a single course of lymphodepleting chemotherapy of fludarabine/cyclophosphamide, followed by the infusion of CD123-CAR T cells. Primary and secondary objectives are evaluated at 4 weeks after infusion. Total study duration is 1 year, at which point patients will enroll on our existing institutional long-term follow-up protocol. If patients achieve disease control post CD123-CAR T-cell therapy, they will be considered for an allogeneic hematopoietic cell transplant (HCT), which is not part of the protocol.
- To determine the safety of one intravenous infusion of escalating doses of autologous, CD123-CAR T cells in patients up to 21 years old with recurrent/refractory CD123+ AML after lymphodepleting chemotherapy.
- To evaluate the antileukemia activity of CD123-CAR T cells.
Treatment inclusion criteria include:
- 21 years old or younger
- Relapsed/refractory CD123+ disease:
- B-ALL relapsed disease that is CD123-positive and CD19 negative/dim or otherwise ineligible for CD19-directed therapies
- Has a suitable HCT donor
- Adequate heart, lung and kidney function
Treatment exclusion criteria include:
- Known primary immunodeficiency
- Acute promyelocytic leukemia
- History of HIV infection
- Received systemic therapy that could interfere with the activity of CD123-CAR T cells in the 14 days prior to CD123-CAR T-cell infusion
- Received rituximab therapy in the 30 days prior to infusion
- Received intrathecal chemotherapy in the 7 days prior to infusion
- Known contraindication to the lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide
St. Jude Children’s Research Hospital
About this study
This study evaluates a new treatment for treatment of acute myelogenous leukemia (AML) and other types of leukemia. This treatment is called CD123-specific CAR T-cell therapy. It is a type of immunotherapy that combines two of the body’s basic disease fighters: antibodies and an immune cell called a T cell.
Doctors usually treat patients with AML with high doses of chemotherapy (anti-cancer medicine) and radiation, followed by a blood cell transplant. CAR T-cell therapy is different. With this treatment, we will change the body’s own immune cells to recognize and kill cancer cells.
In the first step of this study, we will collect immune cells from the patient’s blood. Next, we will insert a gene into the cells so they can recognize a particle that is on the surface of the cancer cell. Those particles are called antigens. If CAR T cells see the antigen on the cancer cell, they will attack and kill it.
The CATCHAML study uses CAR T cells that “see” an antigen called CD123. Once we collect the patient’s immune cells, we will send them to a manufacturing facility on the St. Jude campus to create the CD123-specific CAR T-cell product. Later, the patient will be admitted to the hospital to receive chemotherapy. Following chemotherapy, the patient will receive the CD123-CAR T cells through a vein. This procedure is called infusion. Four weeks after the infusion, we will evaluate the effects of the infused CD123-CAR T cells. At this point, we will decide if the patient should have a bone marrow transplant[SJ3] .
The entire study lasts one year. All patients will be enrolled on a follow-up study for another 14 years.[GS4]
Purpose of this clinical trial
The main purpose of this study is to find the highest dose of CD123-CAR T cells that is safe to give patients with AML. We also want to study the side effects of the treatment and learn how effective it is in fighting this type of cancer.
- 21 years old or younger*
- Relapsed/refractory CD123+ AML, B-ALL, T-ALL or blastic plasmacytoid dendritic cell neoplasm
- Has a suitable bone marrow transplant donor
CATCHAML Quick View Sponsor: St. Jude Children's Research Hospital ClinicalTrials.gov Identifier: NCT04318678 Trial Start Date: May 2020 Estimated Enrollment: 32 Study Type: Interventional Study Phase: Phase 1 Conditions: AML, B-ALL, T-ALL, BPDCN Prinicpal Investigator: Paulina Velasquez, MD
Stephen Gottschalk, MD
Study Sites: St. Jude Children's Research Hospital For a consultation or to discuss CATCHAML: St. Jude Physician/Patient Referral Office