CD123 Redirected T Cells for AML in Pediatric Subjects

Trial details

Who runs it

University of Pennsylvania

Trial code

NCT04678336

Record updated

15 October 2025

Original description

Phase 1 open-label study to evaluate the safety of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).Read full original descriptionShow less

Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD123 Linked to TCRζ and 4-1BB Signaling Domains in Pediatric Subjects With Refractory or Relapsed Acute Myeloid Leukemia

Phase 1 open-label study to evaluate the safety of intravenously administered, lentivirally transduced T cells expressing anti-CD123 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML).

Inclusion: Male and female patients ≥ 1 and ≤ 29 years of age at time of consent; AML in second or greater relapse, post-transplant relapse, or chemotherapy-refractory disease. Specifically:; Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR; Any detectable disease post-allogeneic transplant with flow cytometric confirmation (MRD) of myeloid leukemia of at least 0.1% (as confirmed by Hematologics); OR; Refractory disease, defined as persistent bone marrow involvement with >5% blasts after two courses of induction chemotherapy for patients at initial presentation or >5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR; Subjects must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion; Adequate organ function defined as:; A serum creatinine based on age/gender; Adequate liver function; ALT ≤ 5 x ULN; Total bilirubin ≤ 3 x ULN; ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to AML infiltration of the liver; Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator; Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice; Adequate performance status defined as Lansky or Karnofsky score ≥ 50; Signed informed consent must be obtained; No contraindications for leukapheresis (unless apheresis product previously acquired); Subjects of reproductive potential must agree to use acceptable birth control methods.

Exclusion: Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroids and immunosuppressant medications (including washout requirements prior to CAR T cell administration); Patients with any prior history of myeloproliferative neoplasm; HIV infection; Active hepatitis B or hepatitis C infection; Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy; Any uncontrolled active medical disorder that would preclude participation as outlined; Uncontrolled active infection; Subjects with CNS3 disease that is progressive on therapy or with CNS parenchymal lesions that may increase the risk of CNS toxicity. Subjects with adequately treated CNS leukemia are eligible; Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40); Pregnant or lactating (nursing) women; Patients with relapsed AML with t(15:17); Patients < 6 months from alloHSCT; Patients with somatic JAK2 V617F mutation by PCR or next generation sequencing.

ClinicalTrials.gov NCT04678336