Non-engrafting, CD8 Depleted Donor Lymphocyte Infusion for the Treatment of Myelodysplastic Syndrome after First Therapy or Secondary Acute Myeloid Leukemia

Inclusion Criteria

• Eligible subjects will have MDS and have failed treatment previously with HMAs or AML arising from an antecedent hematologic disorder (AHD) (sAML)
• MDS having failed HMA: * Age 18-79 years, inclusive * Pathologically confirmed MDS or myelodysplastic/myeloproliferative overlap (MDS/MPN) * Revised International Prognostic Scoring System (IPSS-R) score intermediate, high, or very high * Must have failed therapy with an HMA (defined as lack of response by International Working Group [IWG] response criteria or intolerance of the drug)
• sAML: * Pathologically confirmed AML according to World Health Organization (WHO) criteria * Evidence of an antecedent hematologic disorder (AHD) prior to acute leukemia including a known prior diagnosis of MDS, MPN, or MDS/MPN or data suggestive of an AHD such as cytopenias, fibrosis, macrocytic anemia, cellular or dysplasia at or prior to the time of diagnosis. If available, MDS-defining karyotypes (-7/del(7q), -5/del(5q), del(13q), del(11q), del(12p), t(12p), del(9q), idic(X)(q13), t(17p) (unbalanced translocations) or i(17q) (i.e., loss of 17p), t(11;16)(q23;p13.3), t(3;21)(q26.2;q22.1), t(1;3)(p36.3;q21), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34)) or somatic mutations in multiple genes including p53, TET2, JAK2, CALR, MPL, ASXL1, RUNX1, SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 would also confirm eligibility * Age 18-79 years, inclusive * May be previously untreated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Deemed eligible to receive cytotoxic chemotherapy
• Creatinine clearance (CrCl) > 50 ml/min
• Total bilirubin < 2 mg/dL (except for patients with Gilbert’s disease)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)
• Left ventricular ejection fraction >= 50%
• Willing and able to participate in study assessments
• DONOR INCLUSION:
• Age >= 18
• Weight >= 110 pounds
• Hematocrit (HCT) >= 30%
• Platelets (PLT) > 100k
• White blood cells (WBC) >= 3.50k

Exclusion Criteria

• Patients who have had systemic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Hydroxyurea and/or targeted therapies (including but not limited to BCL2 inhibitors, JAK2 inhibitors, FLT3 inhibitors) during this period may be given as a bridging therapy to maintain disease stability while awaiting trial treatment. Intrathecal chemotherapy within this time frame is permitted. Intrathecal chemotherapy may be continued during protocol therapy in order to consolidate or maintain a central nervous system (CNS) remission, but not to treat active CNS disease
• Acute promyelocytic leukemia, or the presence of t(15;17)
• Patients receiving any other investigational agents
• Uncontrolled concurrent illness including, but not limited to, ongoing and uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in the fetus. Breastfeeding should be discontinued if the mother is treated. These potential risks may also apply to other agents used in this study
• Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow-up
• Patients with a poor functional status of ECOG 3-4, or otherwise deemed unfit to tolerate induction chemotherapy
• Patients with blastic transformation of chronic myelogenous leukemia are ineligible
• Exposure to a humanized mouse chimeric antibody within 1 year of starting trial therapy, as this could sensitize patients to components of the CD8 depletion column that may be present in small amounts in the cell product
• Prior allogeneic hematopoietic cell transplant
• DONOR EXCLUSION:
• AB blood type
• Positive testing for or known history of a communicable infectious disease
• Unwilling or unable to provide informed consent
• Has a medical contraindication to blood donation
• Unwilling to donate during business hours, Monday-Friday
• Not suitable for apheresis based on donor safety issues