Nivolumab and Ipilimumab After Donor Stem Cell Transplant in Treating Participants With High Risk Refractory or Relapsed Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of
nivolumab and ipilimumab alone and in combination in patients with high risk or
refractory/relapsed acute myeloid leukemia (AML) following allogeneic stem cell
transplantation (allo-SCT).

II. To evaluate the toxicity of nivolumab and ipilimumab alone and in combination with regard
to the rate and severity of acute graft versus host disease (aGVHD).

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) of nivolumab, ipilimumab and the combination
in patients with high risk or refractory/ relapsed AML following allo-SCT.

II. To determine the duration of response, disease-free survival (DFS), and overall survival
(OS) of patients with high risk or refractory/ relapsed AML treated with this combination
following allo-SCT.

EXPLORATORY OBJECTIVES:

I. To identify neo-antigens, the immune cell phenotype, expression of immune checkpoint
molecules and the T cell receptor (TCR) repertoire following treatment with nivolumab,
ipilimumab and the combination.

II. To study immunological and molecular changes in the peripheral blood and bone marrow in
response to nivolumab and ipilimumab.

III. To investigate the TCR repertoire and immune phenotype in patients who experience aGVHD.

OUTLINE: This is a dose-escalation study. Participants are assigned to 1 of 3 arms.

ARM A: Beginning at least 6 weeks post-stem cell transplant, participants receive nivolumab
intravenously (IV) over 60 minutes on days 1 and 15. Treatment repeats every 28 days for up
to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Beginning at least 6 weeks post-stem cell transplant, participants receive ipilimumab
IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the
absence of disease progression or unacceptable toxicity.

ARM C: Beginning at least 6 weeks post-stem cell transplant, participants receive nivolumab
IV over 60 minutes on days 1, 14, and 28, and ipilimumab IV over 90 minutes on day 1.
Treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, participants are followed up within 30 days and
periodically thereafter.

Inclusion Criteria:

- Patients with morphologic/histologic evidence of relapsed or refractory AML following
allogeneic stem cell transplantation

- Patients must have received preparative regimens to include either
fludarabine/busulfan (area under curve [AUC] >= 5000)/post cyclophosphamide or
fludarabine/melphalan (100 or 140)/post cyclophosphamide

- Patient must have achieved myeloid engraftment as defined by an absolute neutrophil
count >= 500 micro/L on 3 consecutive days

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Total bilirubin =< 2 times upper limit of normal (x ULN) (=< 3 x ULN if considered to
be due to Gilbert's syndrome)

- Aspartate aminotransferase or alanine aminotransferase =< 2.5 x ULN

- Serum creatinine =< 2 x ULN or glomerular filtration rate (GFR) >= 50

- Patients must provide written informed consent

- The interval from the infusion of stem cells to time of initiation of nivolumab or
ipilimumab will be at least 6 weeks (42 days)

- Females must be surgically or biologically sterile or postmenopausal (amenorrheic for
at least 12 months) or if of childbearing potential, must have a negative serum or
urine pregnancy test within 72 hours before the start of the treatment

- Women of childbearing potential must agree to use an adequate method of contraception
during the study and until 3 months after the last treatment. Males must be surgically
or biologically sterile or agree to use an adequate method of contraception during the
study until 3 months after the last treatment

- Fully matched related donor

Exclusion Criteria:

- Patients with known allergy or hypersensitivity to nivolumab or ipilimumab or any of
their components

- Patients with acute GVHD > grade 2 at any time during the post-transplant course

- Patients with a known history of severe interstitial lung disease or severe
pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating
physician

- Patients with a known history of any of the following autoimmune diseases are
excluded:

- Patients with a history of inflammatory bowel disease (including Crohn's disease
and ulcerative colitis)

- Patients with a history of rheumatoid arthritis, systemic progressive sclerosis
(scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g.,
Wegener's granulomatosis)

- Patients with solid organ allografts (such as renal transplant) are excluded

- Ongoing immunosuppressive therapy for the treatment of GVHD. Patients receiving GVHD
prophylaxis will be allowed on this study

- Patients with symptomatic central nervous system (CNS) leukemia at the time of
evaluation or patients with poorly controlled CNS leukemia

- Active and uncontrolled disease/(active uncontrolled infection, uncontrolled
hypertension despite adequate medical therapy, active and uncontrolled congestive
heart failure New York Heart Association [NYHA] class III/IV, clinically significant
and uncontrolled arrhythmia) as judged by the treating physician

- Patients with known human immunodeficiency virus seropositivity will be excluded

- Known to be positive for hepatitis B by surface antigen expression. Known to have
active hepatitis C infection (positive by polymerase chain reaction or on antiviral
therapy for hepatitis C within the last 6 months)

- Any other medical, psychological, or social condition that may interfere with study
participation or compliance, or compromise patient safety in the opinion of the
investigator

- Patients unwilling or unable to comply with the protocol

- Pregnant or breastfeeding