Study of Rituximab and Bendamustine With or Without Brentuximab Vedotin for CD30 Positive Diffuse Large B-cell Lymphoma

Patients will be randomized in a 1:1 manner to receive rituximab plus bendamustine with or
without brentuximab vedotin. Patients who respond to combination treatment containing
brentuximab vedotin and do not experience excessive toxicity may receive additional
single-agent brentuximab vedotin following combination treatment, for up to an additional 10
cycles (up to 16 total cycles of treatment).

Inclusion Criteria:

1. Patients with confirmed CD30-positive DLBCL or grade 3b follicular non-Hodgkin
lymphoma (NHL).

2. Patients must have relapsed or refractory disease following:

1. second-line or greater salvage systemic therapy, or

2. frontline cytotoxic systemic therapy, for patients who are ineligible for stem
cell transplant (SCT).

3. Age 18 years and older.

4. Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET).

5. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

6. Acceptable blood test results.

7. Females of childbearing potential must have a negative pregnancy test result within 7
days prior to the first dose of study drug.

8. Females of childbearing potential and 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 brentuximab vedotin or 12 months following the
last dose of rituximab, whichever is later.

9. Patients must provide written informed consent.

Exclusion Criteria:

1. History of another invasive malignancy that has not been in remission for at least 1
year. (Exceptions are nonmelanoma skin cancer, curatively treated localized prostate
cancer, ductal carcinoma, and cervical carcinoma or a squamous intraepithelial lesion
on PAP smear).

2. History of progressive multifocal leukoencephalopathy (PML).

3. Cerebral/meningeal disease related to the underlying malignancy, unless definitively
treated.

4. Viral, bacterial, or fungal infection within 2 weeks prior to the first dose of
treatment.

5. Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment with
immunotherapy that is not completed 4 weeks prior to first dose of study drug.

6. Females who are pregnant or breastfeeding.

7. Known allergy to any study drug or ingredient contained in the drug formulation of any
of the study drugs.

8. Known to be positive for hepatitis B. Known to have active hepatitis C infection or on
antiviral therapy for hepatitis C within the last 6 months.

9. Known to be positive for human immunodeficiency virus (HIV).

10. Patients with previous allogeneic stem cell transplant.

11. Previous treatment with brentuximab vedotin or bendamustine.

12. Intolerable toxicity to prior rituximab therapy.

13. Current therapy with other investigational agents.

14. Lung disease unrelated to underlying malignancy.

15. History of a stroke or transient ischemic attack, unstable angina, myocardial
infarction, or cardiac symptoms within 6 months prior to the first dose of treatment.

16. Congestive heart failure.

17. Significant peripheral sensory or motor neuropathy at the start of the study.