Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma
Condition: Blastic Plasmacytoid Dendritic Cell Neoplasm; Hepatosplenic T-Cell Lymphoma; HTLV-1 Infection; NK-Cell Lymphoma, Unclassifiable; Primary Systemic Anaplastic Large Cell Lymphoma, ALK-Negative; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Angioimmunoblastic T-cell Lymphoma; Recurrent Enteropathy-Associated T-Cell Lymphoma; Recurrent Mycosis Fungoides; Refractory Adult T-Cell Leukemia/Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Angioimmunoblastic T-cell Lymphoma; Refractory Enteropathy-Associated T-Cell Lymphoma; Refractory Mycosis Fungoides; Refractory Nasal Type Extranodal NK/T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified
MeSH terms: Mycoses; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Mycosis Fungoides; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Extranodal NK-T-Cell; Enteropathy-Associated T-Cell Lymphoma; Intestinal Diseases; Immunoblastic Lymphadenopathy; Recurrence
Intervention: Laboratory Biomarker Analysis; Nivolumab
Intervention description: Correlative studies; Given IV
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well nivolumab works in treating patients with peripheral
      T-cell lymphoma that has come back after a period of improvement or that does not respond to
      treatment. Monoclonal antibodies, such as nivolumab, may block cancer growth in different
      ways by targeting certain cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Relapsed or refractory T-cell lymphoma (TCL) biopsy-proven =< 6 months prior to
             registration, including the following subtypes:

               -  Peripheral T-cell lymphoma, not otherwise specified

               -  Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) negative,
                  primary systemic type

               -  Angioimmunoblastic T-cell lymphoma

               -  Extranodal natural killer (NK)/T-cell lymphoma, nasal type

               -  Adult T-cell lymphoma/leukemia (human T-lymphotropic virus 1 [HTLV1]+)

               -  Blastic NK-cell lymphoma

               -  Enteropathy-associated T-cell lymphoma

               -  Hepatosplenic gamma delta T-cell lymphoma

               -  Transformed mycosis fungoides

               -  T/NK-cell lymphoma, unclassifiable

          -  Measurable disease: subjects must have at least one lesion that is > 15mm (1.5 cm) in
             the longest diameter on cross-sectional imaging and measureable in two perpendicular
             dimensions per computed tomography (spiral CT) or magnetic resonance imaging (MRI)

          -  After failure of allogeneic stem cell transplant (ASCT) or after failure of frontline
             therapy in subjects who declined or are not ASCT candidates

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

          -  White blood cell (WBC) >= 3000/mm^3

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin > 9.0 g/dL

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation due to Gilbert's
             Syndrome

          -  Aspartate transaminase (AST) =< 2.5 x ULN

          -  Creatinine =< 2.0 mg/dL

          -  Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula

          -  Negative serum or urine pregnancy test done =< 7 days prior to registration, for
             persons of childbearing potential only Note: Persons of child-bearing potential
             (POCBP) must use appropriate method(s) of contraception; POCBP should use an adequate
             method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab
             to undergo five half-lives) after the last dose of investigational drug; men who are
             sexually active with POCBP must use any contraceptive method with a failure rate of
             less than 1% per year; men receiving nivolumab and who are sexually active with POCBP
             will be instructed to adhere to contraception for a period of 31 weeks after the last
             dose of investigational product; persons who are not of childbearing potential (ie,
             who are postmenopausal or surgically sterile) as well as azoospermic men do not
             require contraception; should a person become pregnant or suspect being pregnant while
             participating in this study, the person should inform the treating physician
             immediately

          -  Provide written informed consent

          -  Willing to return to enrolling institution for follow-up during the Active Monitoring
             phase of the study

          -  Willing to provide tissue and blood samples for correlative research purposes

        Exclusion Criteria:

          -  All primary cutaneous T-cell lymphomas

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Active, known or suspected autoimmune disease Note: subjects 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

          -  Use of systemic treatment with either corticosteroids (>10 mg daily prednisone
             equivalents) or other immunosuppressive medications < 14 days of registration Note:
             inhaled or topical steroids are permitted; > 10 mg daily prednisone equivalents are
             permitted only in adrenal insufficiency in the absence of active autoimmune disease

          -  Prohibited treatments and or therapies

               -  Autologous stem cell transplant (ASCT) =< 12 weeks prior to first dose of the
                  study drug

               -  Prior treatments (window prior to registration):

                    -  Chemotherapy =< 2 weeks

                    -  Nitrosureas =< 6 weeks

                    -  Therapeutic anticancer antibodies =< 4 weeks

                    -  Radio- or toxin immunoconjugates =< 10 weeks

                    -  Radiation therapy =< 3 weeks

                    -  Or major surgery =< 2 weeks

               -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody,
                  or any other antibody or drug specifically targeting T-cell costimulation or
                  immune checkpoint pathways

                    -  Prior allogeneic stem cell transplant (SCT)

                    -  Chest radiation =< 24 weeks prior to registration

          -  Immunocompromised patients, patients with known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and
             currently receiving antiretroviral therapy, active hepatitis B virus surface antigen
             (HBV sAg+), active hepatitis C (if Ab+ then PCR+) indicating acute or chronic
             infection

          -  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

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Other active malignancy =< 3 years prior to registration EXCEPTIONS: non-melanotic
             skin cancer or carcinoma-in-situ of the cervix NOTE: if there is a history of prior
             malignancy, they must not be receiving other specific treatment for their cancer

          -  Active central nervous system (CNS) involvement or leptomeningeal involvement

          -  History of pancreatitis