Induction Chemo w/ABVD Followed by Brentuximab Vedotin Consolidation in Newly Diagnosed, Non-Bulky Stage I/II Hodgkin Lymphoma

This study is designed as a single arm pilot feasibility trial using an induction of 2-6
cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed
by 6 cycles of brentuximab vedotin (SGN-35) consolidation for previously untreated patients
with stage I and II non-bulky Hodgkin Lymphoma (HL).

Feasibility will be determined by the percentage of patients who have no clinical evidence of
HL, and achieve positron emission tomograph (PET) negative disease post brentuximab
consolidation. We anticipate approximately 40 patients will be eligible across participating
centers (including UNC, Mayo Clinic, and the UNC Cancer Network (UNCCN)) over a 2 year
period. A future phase II study evaluating progression free survival (PFS) after ABVD
followed by brentuximab vedotin will be considered feasible if ≥ 13 of 15 patients enrolled
in this pilot trial become PET negative after brentuximab vedotin consolidation.

Inclusion Criteria:

- Previously untreated stage I or II non-bulky Hodgkin lymphoma

- No mediastinal mass >0.33 maximum intrathoracic diameter on chest x-ray (see
Appendix B)

- No adenopathy ≥7.5 cm in its largest diameter

- Measurable disease as assessed by 2 dimensional measurement by CT (>2cm or 1.5 cm if
0.5 cm slices are used, as in spiral CT scan)

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Age ≥18 years and ≤60 years of age

- Life expectancy of at least 3 months

- Adequate bone marrow function (without transfusion support within one week of
screening) as demonstrated by:

- Hemoglobin ≥ 8 g/dL

- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3

- Platelet count ≥ 75,000/mm3

- Adequate hepatic and renal function as demonstrated by:

- Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)

- Total serum bilirubin ≤1.5 x ULN

- Serum creatinine ≤ 2.0 mg/dL

- Negative serum human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours of
day 1 of treatment with ABVD in women of child-bearing potential

- 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. Effective contraception is
defined as any medically recommended method (or combination of methods) as per
standard of care, including abstinence. Females of non-childbearing potential are
those who are postmenopausal greater than 1 year or who have had a bilateral tubal
ligation or hysterectomy.

- Signed an institutional review board (IRB)-approved informed consent document for this
protocol

Prior to Day 1 of brentuximab vedotin, patients must again meet the following inclusion
criteria:

- Adequate bone marrow function (without transfusion support within one week of D1 of
brentuximab vedotin) as demonstrated by:

- Hemoglobin ≥ 8 g/dL

- Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3

- Platelet count ≥ 75,000/mm3

- Adequate hepatic and renal function as demonstrated by:

- Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)

- Total serum bilirubin ≤1.5 x ULN

- Serum creatinine ≤ 2.0 mg/dL

- Achieved at least a partial response (PR) (and not progressed) after ABVD therapy

Exclusion Criteria:

- Prior therapies for treatment of HL including involved field radiation therapy or any
prior treatment for any malignancy with anthracyclines.

- Bulky disease (defined as a mass measuring > 7.5 cm or one-third the maximal diameter
of the thoracic cavity)

- Known central nervous system (CNS) involvement

- Symptomatic pulmonary disease currently requiring regular medication including but not
restricted to bronchodilators

- Known history of human immunodeficiency virus (HIV), hepatitis B and hepatitis C
(testing is not necessary if patient does not have history of these diseases, and no
risk factors for acquisition of these viruses)

- Cardiac disease with left ventricular ejection fraction of less than 45%

- Known hypersensitivity to any excipient contained in the drug formulation of
brentuximab vedotin or any component of ABVD

- Medical or other condition that would represent an inappropriate risk to the patient
or would likely compromise achievement of the primary study objective

- Other active malignancies with the exception of:

- Non-melanoma skin cancer

- Cervical carcinoma in situ without evidence of disease

- Prostatic intraepithelial neoplasia without evidence of prostate cancer

- Pregnant or lactating women

Prior to Day 1 of brentuximab vedotin, please verify the patient does not meet the criteria
below:

- Symptomatic pulmonary disease currently requiring regular medication including but not
restricted to bronchodilators