Nivolumab in Eliminating Minimal Residual Disease and Maintaining Remission after Donor Stem Cell Transplant in Patients with High Risk Hematologic Malignancies

Inclusion Criteria

• Patients with hematologic malignancies status post allogeneic SCT without evidence of disease relapse, active graft versus host disease (GVHD) or history of more than stage I skin acute GVHD; and off immunosuppression for at least 4 weeks; at least 60 days after allo-SCT
• Patients with high risk myeloid or lymphoid malignancies prior to stem cell transplant with increased risk of disease relapse after stem cell transplant, including but not limited to conditions listed below * Refractory acute myelogenous or lymphoid leukemia * Relapsed acute myelogenous or lymphoid leukemia * Myelodysplastic syndromes with 5% or more blasts or with residual dysplastic changes prior to stem cell transplant, or with poor risk cytogenetic changes, such as -5, -7 or complex karyotype, or with poor molecular mutations, especially p53 mutation * Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase * Recurrent or refractory malignant lymphoma or Hodgkin’s disease with high risk relapse features or not in complete remission * High risk chronic lymphocytic leukemia not in complete remission or with high risk relapse features, such as p53 mutation, or 17p deletion et al. * Acute leukemia (including AML, ALL) with minimal residual disease determined by accepted methods, including multiple color flow cytometry; next generation sequencing (NGS) or molecular testing * Acute leukemia with poor risk cytogenetic changes
• Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status of 0 or 1 (Karnofsky >= 70%)
• Leukocytes >= 1500/mcL, within 14 days prior to treatment
• Absolute neutrophil count >= 500/mcL (in the absence of growth factor support), within 14 days prior to treatment
• Platelets >= 20,000/mcL or recovery to the baseline count (in the absence of transfusion), within 14 days prior to treatment
• Hemoglobin (Hgb) > 9.0 g/dL, within 14 days prior to treatment
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL), within 14 days prior to treatment
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN, within 14 days prior to treatment
• Serum creatinine =< 1.5 x ULN OR creatinine clearance (CrCl) >= 40 mL/min (if using the Cockcroft-Gault formula), within 14 days prior to treatment
• Women of child-bearing potential (WOCBP) 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; WOCBP should use an adequate method to avoid pregnancy for 23 weeks) after the last dose of investigational drug nivolumab; women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab; women must not be breastfeeding; men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception
• Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
• WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational product; men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product; these durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• History of allergy to study drug components
• Patients who have disease relapse, active GVHD or history of more than grade 1 skin acute GVHD, history of chronic (c)GVHD
• Patients with active infection, un-resolving more than grade 2 transplant-related toxicities
• 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 (AEs) due to agents administered more than 4 weeks earlier
• Patients who are receiving any other investigational agents
• Patients with known central nervous system (CNS) involvement may be excluded; however, if CNS disease is cleared before the treatment with nivolumab, patients could be allowed if no permanent CNS damage
• History of severe hypersensitivity reaction to any monoclonal antibody
• 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; breastfeeding should be discontinued if the mother is treated with nivolumab
• Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) might be enrolled if the viral load by PCR is undetectable with/without active treatment and absolute lymphocyte count >= 350/ul
• Patients with a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection might be enrolled if the viral load by PCR is undetectable with/without active treatment
• 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, Sjogren's syndrome 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 should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis should be evaluated for the potential need for additional treatment before coming on study