CART123 + Ruxolitinib in Relapsed/Refractory AML

Inclusion criteria

• 1. Signed informed consent form 2. Male or female age ≥ 18 years. 3. 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 ELN 2022 criteria57 after at least 2 cycles of induction (includes partial remission or refractory/primary refractory disease), OR:
• AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplant).

i. 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 HCT to qualify. Mutations involving DNMT3A, ASXL1 or TET2 should not count as molecular MRD+ disease unless accompanied by other, more specific disease-related molecular or cytogenetic abnormalities.

• Patients with relapsed disease after prior allogeneic 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 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.

• Adequate organ function defined as:
• Estimated creatinine clearance > 35mL/min using the CKD-EPI equation for Glomerular Filtration Rate (GFR); Patients must not be on dialysis
• ALT/AST ≤ 5x 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.

• ECOG Performance Status 0-2.

Exclusion criteria

• 1. Patients with the JAK2 V617F mutation by PCR or next generation sequencing. 2. Patients with signs or symptoms indicative of active CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.

• Patients with relapsed AML with t(15:17). 4. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.

• Active acute or chronic GVHD requiring systemic therapy. 6. 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. For additional details regarding use of steroid and immunosuppressant medications.

• Planned use of fluconazole within the anticipated study treatment window. For additional details on concomitant medication restrictions.

• Receipt of prior CART123 therapy. 11. 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 MS) will be excluded.

• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).