A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)

Prior treatment

• Prior treatment with Brentuximab in the last 6 months or previously refractory to Brentuximab Vedotin (BV) or had progressive disease (PD) while on BV
• Prior hypersensitivity to any component in the ADC formulation
• Treatment with chemotherapy or investigational agents within 2 weeks of start of study treatment

Other illness

• Prior malignancy within the past 3 years except non melanoma skin cancer or other localized cancer treated with curative intent
• Presence of grade \>2 peripheral neuropathy or patients with the demyelinating form of Charcot-Marie-Tooth syndrome.
• History of progressive multifocal leukoencephalopathy (PML)
• Myocardial infarction within the past 6 months
• Patients with the following medical conditions that could affect their participation in the study:
  • any active acute or chronic or uncontrolled infection
  • liver disease including history of viral hepatitis B or C, evidence of cirrhosis, chronic active or persistent hepatitis
  • a known history of HIV
  • symptomatic cardiac disease, including congestive heart failure, coronary artery disease, and arrhythmias

Other

• Anaplastic large cell lymphoma (ALCL) both alk positive and negative
• Cutaneous T cell lymphomas except transformed Mycosis fungoides (MF)
• Pregnancy or breast feeding women
• Presence of central nervous system (CNS) involvement requiring active treatment

• Patients must have histologically or cytologically confirmed relapsed/refractory CD30 low (\<10%) TCL: including peripheral TCL not otherwise specified (PTCL NOS), angioimmunoblastic T cell lymphoma (AITL), hepato-splenic T cell lymphoma (HTCL), adult T cell leukemia/lymphoma (ATLL), enteropathy associated T cell lymphoma (EATL), adult T cell leukemia/lymphoma (ATLL), enteropathy associated T cell lymphoma (EATL), NK T cell lymphoma (NK/TCL)
• At least 1 prior chemotherapy regimen
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. ECOG Performance Status (PS) 3 will be permitted if the decreased PS is attributed to the lymphoma
• Adequate organ function
  • Bilirubin ≤1.5X upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3X ULN even in patients with documented hepatic involvement with lymphoma
  • Serum creatinine clearance ≥30 ml/min
  • Absolute neutrophil count (ANC) ≥1000/μL (unless documented bone marrow involvement with lymphoma)
  • Platelet count ≥50,000/μL (unless documented bone marrow involvement with lymphoma)
• At least 6 weeks from autologous stem cell transplantation
• At least 3 months from allogeneic stem cell transplantation and off immunosuppression and no evidence of graft versus host disease (GVHD)
• Previous treatment with brentuximab vedotin will be allowed if it was done 6 months prior to enrollment and patient was not refractory
• Measurable disease ≥1.5 cm seen on computed tomography (CT) scan and Fluorodeoxyglucose (FDG) avid disease on positron emission Tomography (PET) scan. Splenomegaly measuring \>12 cm, if attributed to TCL and/or positive bone marrow involvement with lymphoma are also eligible.
• Females of childbearing potential must have a negative serum or urine pregnancy test result within 7 days prior to the first dose of study treatment. Women of child-bearing age must agree to use an effective contraception method during the study and for at least 6 months following the last dose of study drug.
• Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document