Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) of ipilimumab or nivolumab administered to
patients with relapsed hematologic malignancies following allogeneic stem cell
transplantation. (Phase I) II. To characterize the toxicity of ipilimumab or nivolumab
administered at the MTD in this patient population. (Phase Ib)

SECONDARY OBJECTIVES:

I. To assess response rate. II. To assess progression free and overall survival.

TERTIARY OBJECTIVES:

I. To assess the phenotypic and functional effects of ipilimumab or nivolumab on immune
cells.

OUTLINE: This is a dose-escalation study.

INDUCTION PHASE: Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1.
Treatment repeats every 21 days for 4 courses in the absence of disease progression or
unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes on day 1. Treatment
repeats every 14 days for 8 courses in the absence of disease progression or unacceptable
toxicity.

MAINTENANCE PHASE: Patients receive ipilimumab IV over 90 minutes. Treatment repeats every 12
weeks beginning at course 5 (24 weeks after the first dose of ipilimumab) for up to 4 courses
in the absence of disease progression or unacceptable toxicity. Patients achieving clinical
benefit will have the option to continue with ongoing maintenance dosing every 12 weeks in
the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab
IV over 30 minutes every 2 weeks in the absence of disease progression or unacceptable
toxicity. Treatment repeats every 14 days for up to a total of 60 weeks (including Induction)
in the absence of disease progression or unacceptable toxicity.

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

Inclusion Criteria:

- Histologically or cytologically confirmed hematologic malignancy

- The following malignancies will be considered eligible if progressive or persistent:

- Chronic lymphocytic leukemia (CLL)

- Non-Hodgkin lymphoma (NHL)

- Hodgkin lymphoma (HL)

- Multiple myeloma (MM)

- Acute leukemia (acute myeloid leukemia [AML], acute lymphoblastic leukemia [ALL])

- Myelodysplastic syndrome (MDS)

- Myeloproliferative neoplasms (MPN)

- Chronic myeloid leukemia (CML)

- Life expectancy of greater than 3 months

- Must have undergone allogeneic hematopoietic stem cell transplantation (HSCT)
(regardless of stem cell source)

- Must have baseline donor T cell chimerism of >= 20%

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

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless due to
Gilbert's disease or disease-related hemolysis, then =< 3.0 x ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 3.0 x institutional ULN

- Creatinine =< 1.5 x institutional ULN

- Prednisone dose =< 5 mg/day and off all other systemic immunosuppressive medications
for at least 4 weeks prior to study entry

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Participants who have had anti-tumor therapy or other investigational agents within 4
weeks prior to registration (6 weeks for nitrosoureas or mitomycin C), or those who
have not recovered from adverse events due to agents administered more than 4 weeks
prior to registration

- Patients with prior history of or active severe (grade 3 or 4) acute graft-versus-host
disease (GVHD)

- Patients with a history of prior treatment with ipilimumab, anti-programmed cell death
protein 1 (PD 1) antibody, or cluster of differentiation (CD)137 agonist therapy are
ineligible for the ipilimumab arm, but are eligible for the nivolumab arm

- Patients who have had donor lymphocyte infusion (DLI) within 8 weeks prior to
registration

- 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

- Patients with known chronic human immunodeficiency virus (HIV), hepatitis B or
hepatitis C infections should be excluded

- 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; 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 or nivolumab administration