Brentuximab Vedotin in Treating Patients With Steroid-Resistant Acute Graft-Versus-Host Disease

PRIMARY OBJECTIVES:

I. Determine whether the complete and partial response rate of steroid-resistant skin GVHD
exceeds 25% after administration of brentuximab vedotin.

SECONDARY OBJECTIVES:

I. Evaluate the effect of brentuximab vedotin on the clinical manifestations of acute GVHD
of the liver and gastrointestinal tract.

II. Determine the incidence and degree of brentuximab vedotin-related toxicity when
administered after allogeneic hematopoietic cell transplantation (HCT).

III. Evaluate cluster of differentiation (CD)30 expression in skin biopsies before and after
administration of brentuximab vedotin.

IV. Enumerate CD30 expressing lymphocytes in the blood and measure the concentration of
soluble CD30 in serum before and after administration of brentuximab vedotin.

V. Determine whether changes in CD30 expression in skin biopsies or blood lymphocytes or the
concentration of CD30 in serum before and after administration of brentuximab vedotin are
correlated with changes in skin GVHD stage.

VI. Evaluate pharmacokinetics (PK) of brentuximab vedotin in patients after allogeneic HCT.

OUTLINE: This is a dose escalation study.

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1, 8, and
15.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Patients with steroid-resistant stage 2 or 3 acute GVHD of the skin with or without
involvement of other organs; patients must have received initial therapy with
prednisone or methylprednisolone at a prednisone-equivalent dose of at least 1.0
mg/kg/day alone or combined with other agents, including psoralen and ultraviolet A
(PUVA), with:

- Flare of rash involving at least 25% of the body surface at any time after
starting prednisone for GVHD treatment, OR

- Rash involving more than 50% of the body surface persisting after at least 1
week of initial treatment, OR

- Rash involving at least 25% of the body surface persisting after at least 2
weeks of initial treatment

- Concomitant use of steroids is permitted; steroid dose should not have been increased
within a week prior to enrollment

- Patient, guardian or legally authorized representative is able and willing to provide
informed consent

- Willing to use effective contraception; both women of childbearing potential and men
who have partners of childbearing potential must agree to use an effective
contraceptive method during the study and for 30 days after the last dose of study
drug

Exclusion Criteria:

- Prior second-line systemic treatment for GVHD

- Absolute neutrophil count (ANC) < 2000/μL

- Administration of growth factor in order to maintain the ANC > 2000/μL

- Platelet count < 30,000/μL, (unsupported)

- Serum total bilirubin concentration > upper limit of normal (ULN)

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3X ULN

- Calculated creatinine clearance < 60 ml/min

- Peripheral neuropathy: clinical total neuropathy score (TNS) score > 2

- Any Grade 3 or higher uncontrolled active infection within 1 week before enrollment

- Bullous formation or desquamation related to GVHD (stage 4 skin GVHD)

- Evidence of recurrent/persistent malignancy by cytogenetics, histology or flow
cytometry

- GVHD after donor lymphocyte infusion (DLI)

- Clinical manifestations of chronic skin GVHD

- Women who are pregnant or lactating; women of childbearing potential must have a
negative serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test
result within 7 days before the first dose of brentuximab vedotin; woman of
non-childbearing potential are those who are postmenopausal greater than 1 year or
who have had a bilateral tubal ligation or hysterectomy

- Patients with a known hypersensitivity to brentuximab vedotin

- History of Progressive multifocal leukoencephalopathy (PML)