Brentuximab Vedotin and Lenalidomide in Patients With Relapsed/ Refractory T-cell Lymphoma or Hodgkin Lymphoma

Inclusion criteria

• Male or female patients of 18 years or older.
• Patient must have a diagnosis of a CD30+ Hodgkin Lymphoma or CD30+ peripheral T-cell lymphoma. Patients with either Hodgkin lymphoma or T-cell lymphoma must have expression of CD30 in ≥10% of lymphoma cells. Patients with CTCL will be considered for inclusion even if CD30 immunohistochemical staining with BerH2 antibody is low or negligible (<10%).

• Peripheral T-cell lymphoma: patients must be considered relapsed or refractory after at least one prior chemotherapeutic regimen or be considered by the investigator to be not suitable for chemotherapy
• Cutaneous T-cell lymphoma: patients must be relapsed or refractory to one prior systemic therapy or be considered by the investigator to be not suitable for chemotherapy
• Patients with Hodgkin lymphoma and one of the following:

i. Relapsed or refractory after at least 2 prior chemotherapy-containing regimens ii.Considered unsuitable for chemotherapy

• Voluntary written informed consent must be given before performance of any study- related procedure.
• Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
• Male patients, even if surgically sterilized, (i.e., status post vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
• Performance status of ECOG ≤2.
• Clinical laboratory values as specified below. Blood tests must be within 10 days of patient registration:

• Absolute neutrophil count >1.5 x109/L, or >1.0 x109/L in the setting of known marrow involvement by tumour.
• Platelet count ≥75x109/L.
• Total bilirubin must be < 1.5 x the upper limit of the normal (ULN) unless the elevation is known to be due to Gilbert syndrome.
• ALT or AST must be < 2.5 x the upper limit of the normal range. AST or ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of haematologic/solid tumor in liver.
• Serum creatinine must be < 150 µmol/L and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute.
• Haemoglobin must be ≥ 80g/L.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy (except alopecia) prior to registration.

Exclusion criteria

• Female patients who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on planned cycle 1, day 1 prior to first dose of study drug.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medication/s, including signs or symptoms of Progressive Multifocal Leucoencephalopathy (PML).
• Any sensory or motor peripheral neuropathy greater than or equal to Grade 2 at registration.
• Known history of any of the following cardiovascular conditions

• New York Heart Association (NYHA) Class III or IV heart failure (see Appendix 18.1).
• Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• A left-ventricular ejection fraction <50%
• Any active systemic viral, bacterial, or fungal infection requiring systemic intravenous antibiotics or systemic antifungal therapies within 2 weeks prior to registration.
• Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives of last dose of that prior treatment.
• Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or lenalidomide.
• Known human immunodeficiency virus (HIV) positive.
• Known hepatitis B surface antigen (HBsAg)-positive, or known or suspected active hepatitis C infection. Patients who are Hepatitis B core antibody positive with no evidence of active disease, i.e.

HBsAg negative/ negative hepatitis B viral load, will still be considered eligible for inclusion, but must receive viral suppressive therapy for the duration of the trial.

• Active systemic malignancy likely to require treatment within the next two years, or previous diagnosis of another malignancy with residual disease. Patients with non-melanoma skin cancer or carcinoma- in-situ of any type are not excluded if they have undergone complete resection.
• Previous exposure to brentuximab vedotin.