A Study of Brentuximab Vedotin, Rituximab, and Dose Attenuated CHP in Elderly Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

This is a multicenter, single-arm pilot study incorporating brentuximab vedotin and dose
attenuated rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) into initial
therapy for elderly patients with DLBCL. Vincristine will be omitted from the standard R-CHOP
regimen given the overlapping toxicities with brentuximab vedotin. CD30 positivity will be
determined at enrollment and patients will be enrolled into a CD30 positive and negative
group in equal numbers. Additionally, a Comprehensive Geriatric Assessment (CGA) will be
performed on all patients, but this will not be used to guide treatment decisions.

Inclusion Criteria:

- Voluntary written informed consent before performance of any study-specific procedure
not part of routine medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care. Subjects must be
able to understand and be willing to sign the written informed consent form.

- Men and women aged greater than or equal to 75 years of age

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3

- Histologically-confirmed DLBCL by World Health Organization classification by site
hematopathologist

- Histologic transformation (HT) will be included on the study. This must be
confirmed with a biopsy. Patients with HT must not have received an
anthracycline-containing regimen in the past.

- Composite lymphoma containing both indolent and large cell features will be
included

- Has received no prior therapy for DLBCL or HT with the exception of a course of
prednisone of less than or equal to 7 days given for lymphoma related symptoms; prior
therapy for follicular lymphoma is accepted, but no prior anthracycline-containing
therapy.

- Carriers of hepatitis B virus should be closely monitored for clinical and laboratory
signs of active hepatitis B virus infection and for signs of hepatitis throughout
study participation.

- Total bilirubin must be less than 1.5 times the upper limit of normal (ULN) unless the
elevation is known to be due to Gilbert syndrome.

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be less than 3
times the upper limit of the normal range. AST and ALT may be elevated up to 5 times
the ULN if their elevation can be reasonably ascribed to the presence of DLBCL in
liver.

Exclusion Criteria:

- Patient has a platelet count of ≤50,000/mm3 within 14 days before enrollment.

- Patient has an absolute neutrophil count of < 1,000/mm3 within 14 days before
enrollment.

- Patient has a calculated or measured creatinine clearance of <30 mL/minute within 14
days before enrollment.

- Patient is receiving peritoneal dialysis or hemodialysis

- Patient has ≥Grade 2 peripheral neuropathy within 14 days before enrollment.

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study.

- New York Heart Association class III heart failure or ejection fraction of less than
30% on echocardiogram or Multi Gated Acquisition Scan (MUGA)

- Patient has received other investigational drugs with 14 days before enrollment

- Prior exposure to anthracycline

- Patient has concomitant active malignancy that the treating physician or PI feels may
interfere with the ability to measure the primary or secondary outcomes

- Patients with a history of curative, surgically treated basal or squamous cell
carcinoma or stage 1 melanoma of the skin or in situ carcinoma of the cervix are
eligible.

- Patients with a malignancy that has been treated with surgery alone with curative
intent will also be excluded, unless the malignancy has been in documented
remission without treatment for ≥ 3 years prior to enrollment.

- Patient is known to be HIV positive (test result not required for enrollment).

- History of solid organ transplantation, or post-transplant lymphoproliferative
disorder

- Patient has history of allogeneic stem cell transplantation.

- History of, or clinically apparent central nervous system (CNS) lymphoma

- Any clinically significant abnormality in screening blood chemistry, hematology, or
urinalysis results that, in the judgment of the investigator, would impede adequate
evaluation of adverse events and/or response to treatment, or that requires aggressive
intervention