The purpose of this study is to determine the efficacy of lenalidomide in the treatment of relapsed or refractory classic Hodgkin lymphoma(cHL).

Hodgkin lymphoma (HL), an uncommon but significant subtype of lymphoma, is divided into classical HL (cHL) and nodular lymphocyte predominant HL (NLPHL). Progress has been made in cHL therapy resulting in 5-year failure free survival rates between 61%-89% even in the setting of advanced stage or bulky disease. Patients who relapse however, have a variable prognosis ranging from a 8-year overall survival rate of less than 8% for patients who never achieve a remission to 54% for patients with a complete remission lasting greater than 12 months. High dose chemotherapy with autologous stem cell support is the standard of care for patients with relapsed cHL but for those that relapse despite aggressive salvage therapy 20 - 50%, with median remission durations of approximately 6 months. Furthermore, a subset of relapsed HL patients may not be candidates for aggressive salvage regimens. These novel salvage therapies are needed for relapsed/refractory cHL, especially agents without serious late toxicities are particularly attractive in this disease. Advances in the understanding of HL pathogenesis and lenalidomide's mechanisms of action provide substantial rationale for evaluating lenalidomide in HL patients.

Inclusion Criteria:

• Histologically documented classical Hodgkin lymphoma that is recurrent or refractory to standard chemotherapy.

• Patients must have relapsed or progressed after at least one prior systemic cytotoxic chemotherapy; prior autologous or allogeneic stem cell transplantation is allowed.

• Measurable disease must be present either on physical examination or imaging studies (CT, MRI, PET/CT). Any tumor mass greater or equal to 1 cm is acceptable.

• Age > 18 years old.

• ECOG performance status of less than or equal to 2 at study entry

• Adequate hematologic, renal, hepatic function as defined by:

  • Absolute neutrophil count greater than or equal to 1000 / uL
  • Platelets greater than or equal to 50,000 / uL
  • Serum creatinine less than or equal to 1.5X institution upper limit of normal (ULN)
  • Total bilirubin less than or equal to 2.0 mg/dL
  • AST (SGOT) and ALT (SGPT) less than or equal to 3 x ULN (if not attributed to cHL)

• Disease free of prior malignancies for greater than or equal to 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

• Understand and voluntarily sign an informed consent form.

• Able to adhere to the study visit schedule and other protocol requirements

• Females of childbearing potential (FCBP)† must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. The two methods of reliable contraception must include one highly effective method (i.e. intrauterine device (IUD), hormonal [birth control pills, injections, or implants], tubal ligation, partner's vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.

• FCBP must have two negative serum or urine pregnancy tests (sensitivity of at least 50 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by RevAssist) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. The subject may not receive study drug until the Investigator has verified that the results of these pregnancy tests are negative.

• Men must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy.

• All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

• Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight

• All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist.

Exclusion Criteria:

• Patients who are candidates for high dose chemotherapy and stem cell transplantation and have not yet undergone stem cell transplantation should not be enrolled.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Any condition, including the presence of laboratory abnormalities.
• Use of any other anti-cancer drug or therapy, including experimental, within 30 days of enrollment.
• Known hypersensitivity to thalidomide.
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Any prior use of lenalidomide.
• Known positive for HIV or infectious hepatitis, type A, B or C.
• Pregnant or breastfeeding females.
• Concurrent use of other anti-cancer agents or treatments.