Nivolumab in Treating Patients With HTLV-Associated T-Cell Leukemia/Lymphoma
Condition: Acute Adult T-Cell Leukemia/Lymphoma; Adult T-Cell Leukemia/Lymphoma; Chronic Adult T-Cell Leukemia/Lymphoma; HTLV-1 Infection; Lymphomatous Adult T-Cell Leukemia/Lymphoma; Smoldering Adult T-Cell Leukemia/Lymphoma
MeSH terms: HTLV-I Infections; Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
Intervention: Laboratory Biomarker Analysis; Nivolumab; Pharmacogenomic Study
Intervention description: Correlative studies; Given IV; Correlative studies
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well nivolumab works in treating patients with human T-cell
      leukemia virus (HTLV)-associated T-cell leukemia/lymphoma. Nivolumab is an antibody, which is
      a type of blood protein that tags infected cells and other harmful agents. Nivolumab works
      against a protein called programmed cell death (PD)-1 and may help the body destroy cancer
      cells by helping the immune system to keep fighting cancer.
    

Eligibility criteria:

        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