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

Trial Status: Active

This phase I trial studies the side effects and best dose of T cell-depleted donor lymphocyte infusion and ipilimumab in treating patients with acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasm, chronic myelomonocytic leukemia, or myelofibrosis that has come back after a donor stem cell transplant. Previously, patients who have relapsed after a donor stem cell transplant have been given infusions of donor white blood cells called donor lymphocyte infusions (DLI) as a way to boost their donor’s immune function and fight the cancer. This immune function can be suppressed by natural anti-inflammatory immune cells (T cells) that are present in the DLI product. Depleting the number of T cells in the DLI product may work better in fighting the cancer. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial determines the highest dose of ipilimumab that can be given safely in several courses and whether ipilimumab may help the donor white blood cells kill the cancer cells.

Inclusion Criteria

  • Histologically or cytologically confirmed relapse of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) (chronic myelomonocytic leukemia [CMML] or myelofibrosis or MDS/MPN with >= 5% blasts in the marrow).
  • Relapse at >= 2 months after first 8/8 HLA-matched HCT.
  • Available original stem cell donor.
  • 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 have had anti-tumor 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 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.


Brigham and Women's Hospital
Status: ACTIVE
Contact: John Koreth
Phone: 617-632-3470
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: John Koreth
Phone: 617-632-3470


I. To determine the safety (maximum tolerated dose [MTD]) of CD25/regulatory T cell (Treg)-depleted donor lymphocyte infusion (DLI) plus ipilimumab in patients with myeloid relapse after matched-hematopoietic cell transplantation (HCT).


I. To determine complete remission (CR/complete remission with incomplete blood count recovery [CRi]) rate at day 43 (6 weeks).

II. To determine the rate of progression-free survival (PFS) and overall survival (OS) at approximately 3 months (day 92) and approximately 1 year (week 60) post cell infusion.

III. To determine the approximate 3 month (day 92) incidence and severity of acute graft versus host disease (GVHD) rates after cell infusion.

IV. To determine the approximate 1 year (week 60) incidence and severity of chronic GVHD rates after cell infusion.


I. To assess the immunologic impact of infusions of CD25/Treg-depleted DLI plus ipilimumab.

II. To correlate clinical response with changes in circulating effector T (Teff) versus (vs.) Treg cell counts and activation.

III. To correlate clinical response with the persistence of adoptively transferred Teff cells.

IV. To correlate clinical response with changes in cytokine and chemokine levels.

V. To correlate clinical response with tumor infiltration by activated CD8+ T cells.

VI. To correlate clinical response with tumor mutation profile, blast phenotype and tumor microenvironment.

VII. To perform tumor neoantigen discovery to identify novel T cell targets and correlate tumor mutational load with response.

OUTLINE: This is a dose-escalation study.

INDUCTION: Patients receive allogeneic CD25/Treg-depleted donor lymphocytes intravenously (IV) over 5-15 minutes and ipilimumab IV over 90 minutes on day 1. Treatment with ipilimumab repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for up to 4 cycles. Patients who show clinical benefit may continue to receive ipilimumab every 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
John Koreth

  • Primary ID 19-142
  • Secondary IDs NCI-2019-03117
  • ID NCT03912064