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

June 25, 2013 updated by: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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

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)

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Partial and complete response rates of steroid-resistant acute skin GVHD following administration of brentuximab vedotin
Time Frame: Up to day 28
Up to day 28

Secondary Outcome Measures

Outcome Measure
Time Frame
Complete and partial response rates of gut and liver acute GVHD after administration of brentuximab vedotin
Time Frame: Up to day 28
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
Time Frame: Assessed up to day 45
Assessed up to day 45

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Merav Bar, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Anticipated)

June 1, 2016

Study Registration Dates

First Submitted

June 7, 2012

First Submitted That Met QC Criteria

June 7, 2012

First Posted (Estimate)

June 12, 2012

Study Record Updates

Last Update Posted (Estimate)

June 27, 2013

Last Update Submitted That Met QC Criteria

June 25, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2589.00
  • NCI-2012-00921 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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