Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

Exclusion Criteria

• •1. Relapsed AML is defined as patients who had a first complete remission (CR) before developing recurrent disease.
• •2. Refractory AML is defined as patients that have not achieved a CR after 2 cycles of standard induction chemotherapy.
• •OR determining the eligibility of the patient. For example, patients who received hypomethylating agents and venetoclax for the treatment of the MDS are not required to receive again hypomethylating agents and venetoclax to treat the secondary AML to be eligible. Similarly, patients who received two lines of therapy for the management of the MDS or MPD are not required to receive an additional two lines of therapy for the management of the AML to be eligible. Patients who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior transplant.
• •Myelodysplastic syndromes (MDS)/Chronic myelomonocytic leukemia (CMML):one of the following:
• •1. Patients with high risk or intermediate risk MDS/CMML who have received at least two lines of therapy and have positive MRD at a level of \>0.1% measured by multiparameter flow cytometry or are not in morphological remission.
• •OR
• •2. Patients with relapse high risk or intermediate risk MDS/CMML after at least 2 lines of therapy. Relapse is defined as positive MRD at a level of \>0.1% measured by multiparameter flow cytometry or loss of morphological remission.
• •OR
• •3. CMML patients with refractory disease defined as failure to achieve complete remission after 4 therapy cycles of hypomethylating agent therapy or relapse or progression after any number of cycles of therapy.
• •4. Patients with MDS/CMML who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior to transplant.
• •1. Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
• •2. Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI.
• •3. Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
• •4. Known active hepatitis B or C.
• •5. Known HIV with detectable viral load
• •6. Presence of active neurological disorder(s).
• •7. Active autoimmune disease within 12 months of enrollment
• •8. Active cerebral or meningeal involvement by the malignancy
• •9. Active (defined as requiring therapy) acute or chronic GVHD
• •10. Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
• •11. Presence of any other serious medical condition that may endanger the patient at investigator discretion.
• •12. Major surgery \<4 weeks prior to first dose of the preparatory chemotherapy
• •13. Allogeneic SCT or DLI \<12 weeks prior to first dose of preparatory chemotherapy
• •14. Concomitant use of other investigational agents.
• •15. Concomitant use of other anti-cancer agents.
• •16. Patients receiving systemic steroid therapy at time of enrollment (physiological substitutive doses deemed per PI assessment are allowed),or have received antithymocyte globulin or lymphocyte immune globulin within 14 days of enrollment or alemtuzumab within 28 days of enrollment.
• •17. Patients receiving immunosuppressive therapy such as steroids and calcineurin inhibitors.
• •Criteria to Receive Lymphodepletion Chemotherapy:
• •Within 72 hours prior to the start of Lymphodepletion chemotherapy, subjects must meet the eligibility criteria outlined below:
• •1. No uncontrolled active systemic infection. Subjects must be fever free for at least 48 hours without antipyretics unless the patient is felt to have tumor fever.
• •2. Absence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by the Principal Investigator.
• •3. Patient should not be receiving systemic steroids above physiologic dosing (excluding dexamethasone 25mg/m\^2 PO as noted in the treatment plan from Day -10 through Day -6.) or calcineurin inhibitors.
• •4. Patients should be at least 7 days from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML patients until the day prior to administration of lymphodepleting chemotherapy.
• •5. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy
• •Criteria Prior to NK Cell Infusion:
• •On Day 0, prior to the NK Cell infusion, subjects must meet the eligibility criteria for infusion outlined
• •1. No active and uncontrolled systemic infection. Subjects must be fever free for 48 hours without antipyretic unless patient is felt to have tumor fever.
• •2. No clinical signs of cardiac failure.
• •3. Oxygen saturation levels (SPO2) \>92%
• •4. No other ongoing medical condition that in the opinion of the investigator can affect patient's safety.
• •5. No rapidly progressing AML/MDS.
• •6. Patient must be able to be off of all steroid treatment within 24hrs of cell infusion.