Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia

Brentuximab vedotin is an antibody with a covalently attached toxin. The antibody portion
targets the protein CD30 on the surface of cells, and the toxin acts against those cells.

PRIMARY OBJECTIVES:

I. To evaluate the response rate to SGN-35 (brentuximab vedotin) in patients with tumor
necrosis factor receptor superfamily, member 8 (CD30+) advanced systemic mastocytosis (SM)
(ASM or mast cell leukemia [MCL] with or without an associated hematological clonal non-mast
cell lineage disease [AHNMD]).

SECONDARY OBJECTIVES:

I. To evaluate the tolerability and safety profile of SGN-35 in patients with SM.

II. To evaluate expression of CD30 on neoplastic mast cells before and during therapy with
SGN-35.

III. To evaluate changes in mastocytosis related symptom scores and quality of life (QOL)
using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).

IV. To evaluate the duration of response (DoR) and time to response (TTR). V. To evaluate
progression-free survival (PFS).

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment
repeats every 21 days for 8 courses in the absence of disease progression or unacceptable
toxicity.

After completion of study treatment, patients are followed up every 6 weeks for 1 year and
then every 12 weeks thereafter.

Inclusion Criteria:

- Written informed consent

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

- Life expectancy > 12 weeks

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
limit of normal (ULN), if caused by ASM/MCL =< 5 x ULN

- Serum direct bilirubin =< 1.5 x ULN; if considered related to ASM/MCL =< 3 x ULN

- Serum creatinine =< 2.0 mg/dL

- A diagnosis of systemic mastocytosis (SM) per 2008 World Health Organization (WHO)
Criteria

- Neoplastic mast cells must express CD30 by immunohistochemistry or flow cytometry

- At least one of the eligible organ damage findings as defined by the international
consensus response criteria

- 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
30 days following the last dose of study drug

- Females of childbearing potential must have a negative serum or urine beta-human
chorionic gonadotropin (hCG) pregnancy test result within 7 days prior to the first
dose of SGN-35

- Females of non-childbearing potential are those who are postmenopausal greater than 1
year or who have had a bilateral tubal ligation or hysterectomy

Exclusion Criteria:

- Unwilling or unable to comply with the protocol

- Any other concurrent severe known disease (except carcinoma in-situ) or concurrent
severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, or active
uncontrolled infection) which could compromise participation in the study

- History of another primary malignancy that has not been in remission for at least 3
years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully
excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and
cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on
Papanicolaou [PAP] smear)

- Cardiovascular disease including congestive heart failure grade III or IV according to
the New York Heart Association (NYHA) classification, left ventricular ejection
fraction of < 50%, myocardial infarction within previous 6 months or poorly controlled
hypertension

- Pregnant or lactating

- Neuropathy greater than or equal to grade 2

- Known hypersensitivity to any excipient contained in the drug formulation

- Confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral
hepatitis

- Presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs
(eg, AML)

- Received any investigational agent, chemotherapy, interferon-alfa, or
2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to Day 1

- Received hematopoietic growth factor support within 14 days of Day 1 of SGN-35

- Use of prednisone (or equivalent corticosteroid dose) for SM up to 10 mg/day or its
equivalent is allowed, but it cannot have been started during screening; patients who
are on prednisone up to 10 mg/day for medical problems unrelated to SM are also
permitted on study

- Presence of FIP1L1-PDGFR-alpha fusion even with resistance to imatinib

- Received any treatment with SGN-35 prior to study entry

- Any surgical procedure within 14 days of Day 1, excluding central venous catheter
placement or other minor procedures (eg, skin biopsy)