Phase I Study of Cell Therapies for the Treatment of Patients With Relapsed or Refractory AML or High-risk MDS

Exclusion Criteria

• •1. Patients with acute promyelocytic leukemia (APL) or EMD-only disease
• •2. Patients with active CNS involvement. Subjects may be cleared of CNS involvement if there has been no evidence of CNS involvement for at least 3 months prior to enrollment. For instance, CSF samples showing no evidence of blasts by CSF cytology, no clinical signs or symptoms, or no radiological findings concerning for CNS involvement.
• •3. Hyperleukocytosis (≥25,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy. (Note: Subjects may be receiving or may receive hydroxyurea to maintain or control hyperleukocytosis)
• •4. Previous treatment with an investigational gene or chimeric antigen receptor therapy (Note: May be permitted after discussion with Medical Monitor)
• •5. Previous treatment with a CD123 directed therapy (T-cell engager or ADC)
• •6. Use of any anti-AML/MDS directed chemotherapy or targeted therapy (except hydroxyurea therapy) or immunosuppressive agents (physiologic doses are allowed), within 14 days or 5 half-lives (whichever is shorter) prior to the date of leukapheresis and use of any anti-AML/MDS directed monoclonal antibody within 28 days prior to date of leukapheresis
• •7. Known infection with Human Immunodeficiency Virus or Human T-Cell leukemia/lymphoma virus type 1 (HTLV-1)
• •8. A known hypersensitivity or severe allergy to study drug components including dimethyl sulphoxide (DMSO) and human serum albumin
• •9. Contraindication to cyclophosphamide or fludarabine
• •10. Subject has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate treatment (Note: Isolated fever may not constitute active infection in and of itself, (e.g., related to disease)
• •11. Severe uncontrolled intercurrent illness including:
• •1. Cardiovascular disease
• •2. Symptomatic congestive heart failure
• •3. Unstable angina, arrythmia, or myocardial infarction (MI) within 6 months prior to screening
• •4. Significant pulmonary dysfunction
• •5. Uncontrolled thromboembolic events or recent severe hemorrhage
• •6. Any history of pulmonary embolism (PE) ever or deep vein thrombosis (DVT) within 3 months of screening. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT if greater than 3 months from time of screening) Note: Central line thrombosis not requiring anticoagulation will not be excluded and will not require a 3-month screening window
• •7. Autoimmune disease
• •12. Seropositive for and with evidence of active hepatitis B or C infection at time of Screening
• •1. Subjects with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months are eligible
• •2. Subjects seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible
• •3. Subjects who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible
• •13. Any sign of active CNS pathology within 6 months of screening including history of epilepsy, seizure requiring anti-seizure medications, paresis, aphasia, stroke, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis. Subarachnoid hemorrhage or central nervous system (CNS) bleed within 3 months of screening
• •14. Subject has active malignant tumors other than AML/MDS that requires active antineoplastic or radiation therapy at the time of screening. Maintenance therapy or hormonal therapy for well-controlled malignancy is allowed
• •15. Females who are pregnant or breastfeeding
• •16. Subjects with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the subject at unacceptable risk are excluded