Brentuximab Vedotin and Lenalidomide for Relapsed or Refractory Diffuse Large B-cell Lymphoma

Inclusion Criteria:

- Relapsed or refractory de novo or transformed DLBCL disease following at least one
prior systemic therapy (for DLBCL).

- CD30 immunohistochemical staining using the anti-CD30 BerH2 antibody must be available
on the most recent biopsy specimen. During dose escalation, patients can be either
CD30 positive or CD30 negative. During dose expansion, 15 patients must be CD30
positive and 15 patients must be CD30 negative.

- Post-ASCT or not a candidate for ASCT. Prior allogeneic stem cell transplant is
allowed if patient is off all immunosuppressives and has no evidence of active GVHD.

- Prior treatment with brentuximab vedotin is allowed provided the patient did not
progress on BV or within 30 days of last dose of BV. Patients must be at least 3
months from the last dose of BV.

- Bidimensional measurable disease of at least 1.5 cm in the greatest transverse
diameter as documented by CT or PET/CT.

- At least 18 years of age.

- ECOG performance status ≤ 2

- Bone marrow and organ function as defined below:

- Absolute neutrophil count (ANC) ≥ 1,000/mcl

- Platelets ≥ 50,000/mcl

- Serum bilirubin ≤ 1.5 x institutional upper limit of normal (IULN) OR serum
bilirubin ≤ 3.0 x IULN for patients with Gilbert's disease or documented hepatic
involvement with NHL

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x IULN
OR ALT and AST ≤ 5.0 x IULN for patients with documented hepatic involvement with
NHL

- Creatinine clearance ≥ 60 mL/min/1.73 m2 as calculated by Cockcroft-Gault

- Women of childbearing potential must follow pregnancy testing requirements as outlined
in the Revlimid REMS® program material. This is defined as either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of
contraception (one highly effective method and one additional effective method AT THE
SAME TIME) at least 28 days prior to the start of lenalidomide, for the duration of
study participation, and for 28 days following the last doses of brentuximab vedotin
and lenalidomide. Women of childbearing potential must also agree to ongoing pregnancy
testing. Men must agree to use a latex condom during sexual contact with a woman of
childbearing potential even if they have had a successful vasectomy. All patients must
be counseled at a minimum of every 28 days about pregnancy precautions and risks of
fetal exposure. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately.

- All study participants must be registered into the mandatory Revlimid REMS® program
and be willing to comply with its requirements. Per standard Revlimid REMS® program
requirements, all physicians who prescribe lenalidomide for research subjects enrolled
into this trial, must be registered in, and must comply with, all requirements of the
Revlimid REMS® program.

- Able to understand and willing to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- Primary mediastinal B-cell lymphoma

- A history of other primary invasive malignancy that has not been in remission for at
least 3 years or a current diagnosis of myelodysplastic syndrome (MDS) or an immature
leukemia such as acute myeloid leukemia (AML).

- Known active cerebral/meningeal lymphoma.

- Present or history of progressive multifocal leukoencephalopathy (PML).

- NYHA Class III or IV congestive heart failure.

- Active CTCAE version 4.03 grade 3 or higher viral, bacterial, or fungal infection.

- Known to be positive for hepatitis B by surface antigen expression and hepatitis B
core antibody.

- Known to have active hepatitis C infection (positive by polymerase chain reaction) or
on antiviral therapy for hepatitis C within 6 months prior to the first doses of
brentuximab vedotin and lenalidomide.

- Known to be positive for HIV.

- Receiving chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with
immunotherapy that is not completed at least 3 weeks prior to study entry, unless
underlying disease is progressing on therapy.

- Currently receiving any other investigational agents.

- Known hypersensitivity to any excipient contained in the drug formulation of
brentuximab vedotin or lenalidomide.

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14
days prior to and again within 24 hours of starting lenalidomide.

- Receiving immunosuppressive therapy.

- Refractory to prior therapy with brentuximab vedotin (evidence of progression within
30 days of the last dose).

- Prior therapy with lenalidomide.