Pembrolizumab and Brentuximab Vedotin in Subjects With Relapsed/Refractory T-cell Lymphoma

Exclusion Criteria

• •1. Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• •2. Patients with adult T-cell leukemia/ lymphoma (ATLL)
• •3. Has received prior systemic anti-cancer therapy including investigational agents ≤ 4 weeks prior to first dose of study treatment on Cycle 1, Day 1. Could consider shorter interval for kinase inhibitors or other short half-life drugs.
• •Note: concurrent use of bexarotene or vorinostat (where the dose has been stable for the 8 weeks prior to initiating therapy on trial) is permitted for CTCL. Concurrent use of topical steroids or therapies for CTCL is allowed.
• •Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or to baseline value (i.e. condition prior to initiation of the therapy associated with the AE). Participants with ≤Grade 2 neuropathy as AE may be eligible.
• •If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• •4. Pregnant or breast-feeding females. A WOCBP who has a positive urine pregnancy test at screening. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• •5. Has received radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• •6. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• •7. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• •8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• •Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• •9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• •10. Has active autoimmune disease that has required systemic treatment in the past one year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• •Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• •11. Active uncontrolled infection requiring systemic therapy (patients must be afebrile for ≥ 48 hours off antibiotics prior to first protocol treatment). If fever is attributed to tumor fever (B symptom) then this criteria would not apply.
• •12. Active myocarditis, regardless of etiology; or New York Heart Association (NYHA) functional classification III-IV heart failure.
• •13. Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• •14. Disease free of prior malignancies for ≥ 1 year with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. (Other malignancies will require advance discussion and agreement between the investigator and the sponsor-investigator regarding risk of recurrence.)
• •15. Known severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• •16. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
• •17. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• •18. Has a history or current evidence of any condition (e.g. renal disease that would preclude treatment or obstructive pulmonary disease and history of bronchospasm), therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •19. Clinically significant history of liver disease, including current alcohol abuse or cirrhosis.
• •20. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •21. Has a known history of active TB (Bacillus Tuberculosis).
• •22. Prior allogeneic stem cell transplant within last 5 years or active graft vs. host disease (GVHD).
• •23. Patients with grade 2 or higher peripheral neuropathy