Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas

Inclusion Criteria

• Pathologically confirmed B- or T-cell lymphomas at the enrolling institution, including stage ≥ Ib CTCL, which has relapsed or progressed after at least one systemic therapy.
• Hodgkin lymphoma is allowed and will be classified as a B-cell lymphoma in the phase IIA portion.
• Age ≥ 18,
• Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment and adverse effects must have resolved to ≤Grade 1 or baseline. In the phase IIa portion, in progressing subjects, a 2 week washout may be allowed after discussion with the MSK Principal Investigator.
• Previous radiation, hormonal therapy, and/or surgery must have been discontinued or completed at least 2 weeks prior to treatment in this study and adverse effects must have resolved. Lymph node or other diagnostic biopsies within 2 weeks are not considered exclusionary.
• ECOG ≤ 2
• Meet the following laboratory criteria:
• Absolute neutrophil count 1.0/mm³,
• Platelet count 80 K/μ (in the Phase II portion, if thrombocytopenia is due to bone marrow involvement platelet count must be 50 K/μL),
• Phase Ib subjects must have calculated creatinine clearance 50ml/min by Cockcroft-Gault formula, phase IIa subjects must have calculated creatinine clearance ≥ 40ml4/min by Cockcroft-Gault formula.
• Total bilirubin 1.5 x upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) 3 x ULN
• Measurable disease for phase IIa portion only.
• Lymphoma (includes CTCL patients who are without evidence of the disease in the skin): CT or PET/CT by modified Cheson criteria with incorporation of PET.
• CTCL: mSWAT >0, or absolute Sezary count ≥ 1000 cells/μL.
• All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMS ® program.
• Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication ( 3 weeks may be continued (CTCL only).
• Women of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
• A female of reproductive potential is a sexually mature female who:
• has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).

Exclusion Criteria

• Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded. For eligibility on this trial, allogeneic stem cell transplantation is not to be considered a standard curative option.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
• Pregnant females. (Lactating females must agree not to breast feed while taking carfilzomib, lenalidomide or romidepsin).
• Known hypersensitivity to thalidomide.
• The development of erythema multiforme if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Prior use of lenalidomide if discontinued due to toxicity.
• Prior therapy with romidepsin if discontinued due to toxicity.
• Prior therapy with carfilzomib if discontinued due to toxicity.
• Prior therapy with a proteasome inhibitor if discontinued due to toxicity.
• Concurrent use of other anti-cancer agents or treatments.
• Known seropositive and requiring anti-viral therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Concurrent malignancy requiring active therapy.
• Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
• Known central nervous system