Nivolumab in Treating Patients With HTLV-Associated T-Cell Leukemia/Lymphoma

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of nivolumab for patients with HTLV-associated
adult T-cell leukemia lymphoma (ATLL).

II. To determine the efficacy of nivolumab for patients with HTLV-associated ATLL.

SECONDARY OBJECTIVES:

I. To determine effects of nivolumab on HTLV-1 proviral deoxyribonucleic acid (DNA) and
ribonucleic acid (RNA) loads.

II. To determine the effects of nivolumab on anti-HTLV-1 and anti-ATLL immune responses.

III. To determine effects of nivolumab on HTLV-1 integration site clonality.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats
every 14 days for 46 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Inclusion Criteria:

- Patients with any stage of pathologically confirmed cluster of differentiation (CD)3+
acute, lymphoma, chronic, or smoldering subtypes of ATLL

- Documentation of HTLV infection (enzyme linked immunosorbent assay [ELISA]) in
individual with confirmation of HTLV-1 infection (by immunoblot or polymerase chain
reaction [PCR]) or a consistent clinical picture (including two of the following: 1)
CD4+ leukemia or lymphoma, 2) hypercalcemia, and/or 3) Japanese, Caribbean or South
American birthplace)

- Patients with acute or lymphoma forms must have received at least one cycle of
combination chemotherapy (with or without mogamulizumab) or interferon (with or
without zidovudine and/or arsenic); individuals with chronic or smoldering acute
T-cell lymphoma (ATL) are not required to have had prior treatment or could have
received any number of previous courses of therapy

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 60%)

- Life expectancy > 12 weeks

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; or abstinence) prior to study entry and
for the duration of study participation; women should continue birth control for 23
weeks after stopping nivolumab, and men should continue birth control for 31 weeks
after stopping nivolumab; should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, 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 31 weeks after completion of nivolumab administration

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

Exclusion Criteria:

- Patients who have had 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

- Patients who are receiving any other investigational agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to nivolumab

- Prior allogeneic transplantation

- 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

- Any condition requiring > 10 mg/d prednisone equivalents

- Current or prior HTLV-1 associated inflammatory diseases, including but not limited to
myelopathy, uveitis, arthropathy, pneumonitis, or a Sjogren's disease-like disorder

- Prior treatment with anti-PD-1, anti-programmed death-ligand (PD-L)1, anti-PD-L2
antibody

- Grade 2 or greater toxicity from prior therapy

- Grade 2 or greater diarrhea

- Patients with active autoimmune disease or history of autoimmune disease that might
recur, which may affect vital organ function or require immune suppressive treatment
including systemic corticosteroids, should be excluded; these include but are not
limited to patients with a history of immune related neurologic disease, multiple
sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia
gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE),
connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's,
ulcerative colitis, hepatitis; and patients with a history of toxic epidermal
necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be
excluded; patients with vitiligo, endocrine deficiencies including thyroiditis managed
with replacement hormones including physiologic corticosteroids are eligible; patients
with rheumatoid arthritis and other arthropathies (other than HTLV-associated
arthropathy), and psoriasis controlled with topical medication and patients with
positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies
should be evaluated for the presence of target organ involvement and potential need
for systemic treatment but should otherwise be eligible; patients are permitted to
enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, psoriasis not requiring
systemic treatment, or conditions not expected to recur in the absence of an external
trigger (precipitating event)

- Patients who have had evidence of active or acute diverticulitis, intra-abdominal
abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are
known risk factors for bowel perforation should be evaluated for the potential need
for additional treatment before coming on study

- Patients who have hepatitis C (both reactive anti-hepatitis C virus [HCV] antibody and
detectable HCV RNA) and hepatitis B (hepatitis B surface antigen [HBsAg] positive and
anti-hepatitis B core [HBc]-total positive), may be enrolled, provided their total
bilirubin: =< 1.5 x institutional upper limit of normal (ULN) AST (SGOT)/ALT (SGPT):
=< 2.5 x institutional upper limit of normal

- Patients with concurrent human immunodeficiency virus (HIV) infection may be enrolled
if compliant with 3 or more drug anti-retroviral regimen and virus load less than 50
copies/ml and CD4 count greater than 250 cells/ml, and no concurrent opportunistic
infection or other malignancy

- Any other prior malignancy from which the patient has been disease free for less than
3 years, with the exception of adequately treated and cured basal or squamous cell
skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other
cancer

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with nivolumab