T Cell-Depleted Donor Lymphocyte Infusion and Ipilimumab in Treating Patients with Myeloid Disease Relapse after Donor Stem Cell Transplant

Inclusion Criteria

• Histologically or cytologically or molecularly confirmed relapse of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) including chronic myelomonocytic leukemia (CMML), myelofibrosis or MDS/MPN. Disease relapse includes patients with myeloid blasts by flow and/or morphology in marrow or extramedullary disease sites; or persistence and/or recurrence of disease defining mutations.
• Relapse at >= 2 months after any 8/8 or better HLA-matched HCT.
• Available original stem cell donor.
• Age >= 18 years. Because no dosing or adverse event data are currently available on the use of ipilimumab in participants < 18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky performance status >= 60).
• Recipient donor T cell chimerism >= 20% within 4 weeks prior to cell infusion.
• < 50% bone marrow involvement within 4 weeks prior to cell infusion.
• No systemic corticosteroid therapy for GVHD (=< 5 mg of prednisone or equivalent doses of other systemic steroids for non-GVHD, non-autoimmune indications for at least 4 weeks prior to cell infusion).
• No other systemic medications/treatments (e.g. extracorporeal photopheresis [ECP]) for GVHD for at least 4 weeks prior to cell infusion.
• Ability to understand and willingness to sign written informed consents.
• Total bilirubin: =< 1.5 x institutional upper limit of normal (ULN) (except Gilbert’s or disease-related hemolysis, then < 3 x ULN).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): =< 3 x institutional ULN.
• Creatinine clearance: =< 1.5 x institutional ULN.
• Oxygen (O2) saturation: >= 90% on room air.
• Left ventricular ejection fraction (LVEF) > 40%.
• The effects of CD25/Treg-depleted DLI and ipilimumab on the developing human fetus are unknown. For this reason and because immunomodulatory agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or within 23 weeks after the last dose of study drug, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for at least 31 weeks after completion of ipilimumab administration.
• Negative pregnancy test for females of childbearing potential only.

Exclusion Criteria

• Extramedullary relapse involving immuno-privileged sites (e.g. central nervous system [CNS], testes, eyes). Other sites of extramedullary relapse (e.g. leukemia cutis, granulocytic sarcoma) are acceptable.
• Participants who had cytotoxic chemotherapy or other investigational agents within 4 weeks prior to cell infusion (6 weeks for nitrosoureas or mitomycin C), or immunotherapy within 8 weeks prior, or those who have not recovered from adverse events due to agents administered more than 4 weeks prior. Use of hydroxyurea, hypomethylating agents (HMAs) (e.g. azacytidine, decitabine) and/or approved novel agents (e.g. venetoclax, FLT3 inhibitors, IDH1/2 inhibitors etc.) to control counts within 4 weeks prior to cell infusion is permitted.
• Prior history of DLI.
• Prior history of treatment with anti-CTLA-4 or anti-PD-1 pathway therapy, or CD137 agonist therapy.
• Prior history of severe (grade 3 or 4) acute GVHD, or ongoing active GVHD requiring systemic treatment.
• Organ transplant (allograft) recipient.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Ipilimumab or other agents used in study.
• Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn’s Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener’s granulomatosis]) and motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre syndrome and myasthenia gravis). Patients with Hashimoto’s thyroiditis are eligible to go on study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active 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 of the unknown teratogenic risk. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated on this study.
• Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with agents used in this study. In addition, these participants are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment related hepatotoxicity after HCT.