Acute Myeloid Leukemia Clinical Trial
CD123 Redirected T Cells for AML in Pediatric Subjects
Phase 1 open-label study to estimate the safety, manufacturing feasibility, and efficacy 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).
This is a Phase 1 study to determine the safety, manufacturing feasibility, and efficacy of CART123 cells following lymphodepleting chemotherapy in pediatric subjects with relapsed/refractory AML.
Subjects will receive CART123 cells via a single IV infusion at a dose of 2x10^6 CART123 cells/kg, following lymphodepleting chemotherapy. The total dose administered to each subject will be based on the subject's body weight obtained at the time of apheresis. The minimum acceptable dose for infusion is 1x10^5 CART123 cells/kg.
There will be a 28-day stagger between the first 3 subject infusions, such that the next subject may not receive treatment (lymphodepleting chemotherapy plus CART123 cells) until the previous subject has completed their Day 28 safety follow-up visit and a DLT assessment has been performed. Subsequent infusions will be staggered by a minimum of 14 days.
It is recommended that subjects with marrow aplasia at Day 28+/-5 undergo an allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy. If required, this procedure will be performed as part of routine care, outside of the scope of this research study; however, subjects will continue to be followed onstudy. All subjects must, therefore, have a previously identified stem cell donor as part of their eligibility to participate in this study.
All subjects will be followed monthly for up to 6 months after the CART123 cell infusion (Day 0). Thereafter, subjects will be transitioned into LTFU for up to 15 years post infusion.
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%; 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 available who may donate cells in the event the subject needs to undergo an allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria; donors must be fully cleared to proceed as the donor.
Adequate organ function defined as:
a. A serum creatinine based on age/gender b. 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 ALL 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.
Pregnant or lactating (nursing) women.
Patients with relapsed AML with t(15:17).
Patients must be > 6 months from alloHSCT.
Active hepatitis B or hepatitis C infection.
Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
Concurrent use of systemic steroids at the time of cell infusion or cell collection or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
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.
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There is 1 Location for this study
Philadelphia Pennsylvania, 19104, United States
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