CART123 + Ruxolitinib in Relapsed/Refractory AML

Eligibility 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:
• 1. 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:
• 2. AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplant).
• 4. 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).
• 5. 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.
• 6. Adequate organ function defined as:
• 1. Estimated creatinine clearance \> 35mL/min using the CKD-EPI equation for Glomerular Filtration Rate (GFR); Patients must not be on dialysis
• 2. ALT/AST ≤ 5x upper limit of normal range
• 3. Direct bilirubin ≤ 2.0 mg/dl, unless the subject has Gilbert's syndrome (≤3.0 mg/dl)
• 4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen \> 92% on room air
• 5. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by transthoracic echocardiography or MUGA scan.
• 7. ECOG Performance Status 0-2.
• * 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.
• 3. Patients with relapsed AML with t(15:17). 4. Active hepatitis B, active hepatitis C, or other active, uncontrolled infection.
• 5. Active acute or chronic GVHD requiring systemic therapy. 6. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• 7. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• 8. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
• 9. Planned use of fluconazole within the anticipated study treatment window. For additional details on concomitant medication restrictions.
• 10. Receipt of prior CART123 therapy. 11. Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.
• 12. Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• 13. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).