Status:
TERMINATED
CD123 Redirected T Cells for AML in Pediatric Subjects
Lead Sponsor:
University of Pennsylvania
Conditions:
Acute Myeloid Leukemia, in Relapse
Acute Myeloid Leukemia, Pediatric
Eligibility:
All Genders
1-29 years
Phase:
PHASE1
Brief Summary
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 /...
Detailed Description
This is a Phase 1 study designed to evaluate the safety, feasibility, and preliminary efficacy of CART123 cells in pediatric subjects with relapsed/refractory Acute Myeloid Leukemia (AML). The study w...
Eligibility Criteria
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
- i. ALT ≤ 5 x ULN
- ii. Total bilirubin ≤ 3 x ULN
- iii. 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.
- c. 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
- d. 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
- Pregnant or lactating (nursing) women.
- Patients with relapsed AML with t(15:17).
- Patients \< 6 months from alloHSCT.
- HIV infection.
- Active hepatitis B or hepatitis C infection.
- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
- 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).
- 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).
- Patients with any prior history of myeloproliferative neoplasm.
- Patients with somatic JAK2 V617F mutation by PCR or next generation sequencing.
Key Trial Info
Start Date :
April 2 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 9 2025
Estimated Enrollment :
12 Patients enrolled
Trial Details
Trial ID
NCT04678336
Start Date
April 2 2021
End Date
May 9 2025
Last Update
October 15 2025
Active Locations (1)
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1
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104