CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
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|ClinicalTrials.gov Identifier: NCT04318678|
Recruitment Status : Recruiting
First Posted : March 24, 2020
Last Update Posted : August 13, 2021
The CD123-CAR T-cell therapy is a new treatment that is being investigated for treatment of AML, T-ALL, B-ALL or 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.
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, B-ALL, T-ALL or BPDCN) after lymphodepleting chemotherapy.
To evaluate the antileukemia activity of CD123-CAR T cells.
- 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
|Condition or disease||Intervention/treatment||Phase|
|AML B-ALL T-ALL BPDCN||Drug: CD123-CAR T Drug: Cyclophosphamide Drug: Fludarabine Drug: Mesna Drug: Rituximab||Phase 1|
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.
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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)|
|Actual Study Start Date :||May 27, 2020|
|Estimated Primary Completion Date :||July 1, 2024|
|Estimated Study Completion Date :||July 1, 2025|
CD123-CAR T cell therapy
CD123-CAR T-cell dose and infusion Up to 4 Dose levels will be evaluated with a maximum dose of 2.5 x 10^8 CAR+ T cells. If dose limiting toxicities (DLTs) are observed on Dose level 1 then the cell dose is de- escalated.
Drug: CD123-CAR T
To treat relapsed/refractory CD123+ AML, B-ALL, T-ALL or BPDCN patient population that needs new cancer-directed therapies.
Other Name: CD123-CAR T cells
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.
Other Name: Cytoxan
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
Other Name: Fludara
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
Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes
Other Name: Rituxan
- Maximum tolerated dose of CD123-CAR T cells (CATCHAML) [ Time Frame: 4 weeks after CD123-CAR T-cell infusion ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04318678
|Contact: Paulina Velasquez, MDfirstname.lastname@example.org|
|United States, Tennessee|
|St. Jude Children's Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Paulina Velasquez, MD 866-278-5833 email@example.com|
|Principal Investigator: Paulina Velasquez, MD|
|Principal Investigator:||Paulina Velasquez, MD||St. Jude Children's Hospital|