Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma

Inclusion Criteria

• Male or female patients aged ≥ 16 years
• Life expectancy > 12 weeks
• ECOG (eastern oncology cooperative group) performance status ≤ 2
• Relapsed or refractory* peripheral T-cell lymphoma including the following histologies: peripheral T-cell lymphoma not otherwise specified (PTCL NOS) , angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), enteropathy associated T-cell lymphoma (EATL), extranodal NK (natural killer)/T- cell lymphoma (ENKL), transformed mycosis fungoides (LCT MF), hepatosplenic T-cell lymphoma (HSTCL) * For all relapsed patients, relapse must be confirmed by tissue biopsy (or bone marrow trephine if no other tissue available). For refractory patients, a biopsy must have been obtained within the last 3 months
• Failed at least 1 prior therapy (but no upper limit of prior regimens)
• Adequate haematological function defined by at registration:
• absolute neutrophil count (ANC) ≥ 1.0 × 109/L, (unsupported)
• platelet count ≥ 75 × 109/L, (unsupported)
• haemoglobin ≥ 9 g/dL (may have been transfused)
• Adequate hepatic function defined by:
• total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range
• AST (aspartate aminotransferase) or ALT (alanine aminotransferase) levels ≤ 2.5 × ULN for all patients, or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver)
• Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
• CT measurable disease with at least 1 lesion having short axis > 1.5cm or splenomegaly > 14cm in cranio-caudal length attributable to relapsed/non responding lymphoma
• Negative serum pregnancy test at screening for women of childbearing potential.
• Highly effective contraception for both male and female patients if the risk of conception exists. (Note: women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required from consent, throughout and for at least 60 days after avelumab treatment.
• Ability to give informed consent

Exclusion Criteria

Patients are not eligible for the trial if they fulfill any of the following exclusion criteria:

• All patients with active central nervous system (CNS) involvement of lymphoma
• Prior organ transplantation, including allogeneic stem cell transplantation
• Significant acute or chronic infections including, among others:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS),
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
• Current use of immunosuppressive medication, EXCEPT for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); Systemic corticosteroids at a maximum dose of ≤ 1 mg/kg of prednisone or equivalent during screening (to be stopped by day 1 of trial treatment); Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
• Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable are acceptable
• Pregnancy or la