A Phase II Study of the Combination of Azacitidine and Pembrolizumab for Patients Relapsed/Refractory Hodgkin's Lymphoma

Inclusion Criteria:

• HL patients with relapse or progression. Prior checkpoint inhibitors will be allowed

• Patients with relapsed HL involving extranodal sites

• HL patients who are not regarded as a candidate for high-dose, conventionalchemotherapy

• Age of enrollment: Minimum age 1 year. No maximum age, study will include anyone inthe pediatric/adolescent center at MD Anderson (MDA)

• Eastern Cooperative Oncology Group (ECOG) performance status =< 3 or Lanskyperformance status >= 50

• Adequate renal function per age unless related to the disease

• Total bilirubin < 2 x upper limit of normal (ULN) unless increase is due toGilbert's disease

• Aspartate Aminotransferase (AST) < 3 x ULN unless considered due to lymphomainvolvement

• Provision of written informed consent or assent as per MD Anderson Cancer Center (MDACC) policy for study subjects

• Females must be surgically or biologically sterile or if of childbearing potential,must have a negative serum or urine pregnancy test within 72 hours before the startof the treatment and each subsequent dose

• Women of childbearing potential must agree to use an adequate method ofcontraception during the study and until 4 months after the last treatment. Malesmust be surgically or biologically sterile or agree to use an adequate method ofcontraception during the study until 1 month after the last treatment

• Males need to inform the doctor right away if the partner becomes pregnant orsuspects pregnancy. While in this study and for 30 days after the last treatment thepatient should not donate sperm for the purposes of reproduction. He will need touse a condom while in this study and for 30 days after the last treatment

Exclusion criteria:

• Allergy to azacitidine or pembrolizumab or the drugs' components

• Active and uncontrolled comorbidities including active uncontrolled infection,uncontrolled hypertension despite adequate medical therapy, active and uncontrolledcongestive heart failure New York Heart Association (NYHA) class III/IV, clinicallysignificant and uncontrolled arrhythmia as judged by the treating physician

• Patients with known infection with human immunodeficiency virus (HIV) or activeHepatitis B or C

• Any other medical, psychological, or social condition that may interfere with studyparticipation or compliance, or compromise patient safety in the opinion of theinvestigator

• Pregnant or breastfeeding

• Has received a live vaccine within 30 days of planned start study therapy

• Current or prior use of immunosuppressive medication within 14 days prior to thefirst dose of pembrolizumab. The following are exceptions to this criterion:

• Intranasal, inhaled, topical steroids, or local steroid injections (eg,intra-articular injection)

• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day ofprednisone or equivalent

• Steroids as premedication for hypersensitivity reactions (eg, computedtomography [CT] scan premedication)

• Active or prior documented autoimmune disease (including inflammatory bowel disease,celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhoodatopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, orpsoriasis not requiring systemic treatment (within the past 2 years) are notexcluded

• Has known active central nervous system metastases and/or carcinomatous meningitis