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

Primary Purpose

Graft Versus Host Disease

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
brentuximab vedotin
laboratory biomarker analysis
pharmacological study
Sponsored by
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Graft Versus Host Disease

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive care (brentuximab vedotin)

Arm Description

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

Outcomes

Primary Outcome Measures

Partial and complete response rates of steroid-resistant acute skin GVHD following administration of brentuximab vedotin

Secondary Outcome Measures

Complete and partial response rates of gut and liver acute GVHD after administration of brentuximab vedotin
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

Full Information

First Posted
June 7, 2012
Last Updated
June 25, 2013
Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01616680
Brief Title
Brentuximab Vedotin in Treating Patients With Steroid-Resistant Acute Graft-Versus-Host Disease
Official Title
Phase II Study to Evaluate the Efficacy of Brentuximab Vedotin in Patients With Steroid-Resistant Acute GVHD
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Withdrawn
Study Start Date
September 2012 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. 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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Supportive care (brentuximab vedotin)
Arm Type
Experimental
Arm Description
Patients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15.
Intervention Type
Drug
Intervention Name(s)
brentuximab vedotin
Other Intervention Name(s)
Adcetris, anti-CD30 ADC SGN-35, anti-CD30 antibody-drug conjugate SGN-35, antibody-drug conjugate SGN-35, SGN-35
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Partial and complete response rates of steroid-resistant acute skin GVHD following administration of brentuximab vedotin
Time Frame
Up to day 28
Secondary Outcome Measure Information:
Title
Complete and partial response rates of gut and liver acute GVHD after administration of brentuximab vedotin
Time Frame
Up to day 28
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merav Bar
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

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

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