Genetically Engineered Cells (CART123) in Combination with Ruxolitinib for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria

• Signed informed consent form.
• Male or female age ≥ 18 years.
• Patients with active acute myeloid leukemia (AML) with no available curative treatment options using currently available therapies. This is specifically defined as one of the following: * AML that has not achieved a complete remission or morphologic leukemia free state by European LeukemiaNet (ELN) 2022 criteria after at least 2 cycles of induction (includes partial remission or refractory/primary refractory disease), OR: * AML relapsed following allogeneic stem cell transplantation (including myelodysplastic syndromes [MDS] evolved to AML post-allogeneic stem cell transplant). ** Note: Morphologic relapse is not required; Patient may have persistent/recurrent disease-associated molecular, phenotypic or cytogenetic abnormalities (i.e., MRD) at any time after allogeneic hematopoietic cell transplantation (HCT) to qualify. Mutations involving DNMT3A, ASXL1 or TET2 should not count as molecular MRD positive (+) disease unless accompanied by other, more specific disease-related molecular or cytogenetic abnormalities.
• Patients with relapsed disease after prior allogeneic stem cell transplant (SCT) must be at least 3 months from transplantation (where receipt of the stem cell product is defined as day 0) and must not require systemic immunosuppression (for prevention or treatment of graft versus host disease [GVHD]).
• Patients must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion if clinically indicated. Donor may be matched or mismatched and must be found to be suitable according to the institution’s standard criteria.
• Estimated creatinine clearance > 35mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for glomerular filtration rate (GFR); Patients must not be on dialysis.
• Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 5 x upper limit of normal range.
• Direct bilirubin ≤ 2.0 mg/dl, unless the subject has Gilbert's syndrome (≤ 3.0 mg/dl).
• Must have a minimum level of pulmonary reserve defined as ≤ grade 1 dyspnea and pulse oxygen > 92% on room air.
• Left ventricle ejection fraction (LVEF) ≥ 40% confirmed by transthoracic echocardiography or MUGA scan.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria

• Patients with the JAK2 V617F mutation by polymerase chain reaction (PCR) or next generation sequencing.
• Patients with signs or symptoms indicative of active central nervous system (CNS) involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.
• Patients with relapsed AML with t(15:17).
• Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
• Active acute or chronic GVHD requiring systemic therapy.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Dependence on systemic steroids or immunosuppressant medications.
• Planned use of fluconazole within the anticipated study treatment window.
• Receipt of prior CART123 therapy.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as multiple sclerosis [MS]) will be excluded.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and dextran 40).