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

Sponsor

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01616680

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

The purpose of this research is to test the safety and efficacy of brentuximab vedotin in patients with acute skin graft-versus-host disease (GVHD)

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease	Drug: brentuximab vedotin Other: laboratory biomarker analysis Other: pharmacological study	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

Evaluate the effect of brentuximab vedotin on the clinical manifestations of acute GVHD of the liver and gastrointestinal tract.
Determine the incidence and degree of brentuximab vedotin-related toxicity when administered after allogeneic hematopoietic cell transplantation (HCT).
Evaluate cluster of differentiation (CD)30 expression in skin biopsies before and after administration of brentuximab vedotin.
Enumerate CD30 expressing lymphocytes in the blood and measure the concentration of soluble CD30 in serum before and after administration of brentuximab vedotin.
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.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Phase II Study to Evaluate the Efficacy of Brentuximab Vedotin in Patients With Steroid-Resistant Acute GVHD

Study Start Date :

Sep 1, 2012

Anticipated Primary Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Supportive care (brentuximab vedotin) Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15.	Drug: brentuximab vedotin Given IV Other Names: Adcetris anti-CD30 ADC SGN-35 anti-CD30 antibody-drug conjugate SGN-35 antibody-drug conjugate SGN-35 SGN-35 Other: laboratory biomarker analysis Correlative studies Other: pharmacological study Correlative studies Other Names: pharmacological studies

Arm

Intervention/Treatment

Experimental: Supportive care (brentuximab vedotin)

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

Drug: brentuximab vedotin

Given IV

Other Names:

Adcetris

anti-CD30 ADC SGN-35

anti-CD30 antibody-drug conjugate SGN-35

antibody-drug conjugate SGN-35

SGN-35

Other: laboratory biomarker analysis

Correlative studies

Other: pharmacological study

Correlative studies

Other Names:

pharmacological studies

Outcome Measures

Primary Outcome Measures

Partial and complete response rates of steroid-resistant acute skin GVHD following administration of brentuximab vedotin [Up to day 28]

Secondary Outcome Measures

Complete and partial response rates of gut and liver acute GVHD after administration of brentuximab vedotin [Up to day 28]
Incidence and severity of brentuximab vedotin-related toxicity after allogeneic HCT defined graded according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 4 [Assessed up to day 45]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)