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

This study is currently recruiting participants.
Verified March 2013 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01616680
First received: June 7, 2012
Last updated: March 5, 2013
Last verified: March 2013
History of Changes
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Partial and complete response rates of steroid-resistant acute skin GVHD following administration of brentuximab vedotin [ Time Frame: Up to day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete and partial response rates of gut and liver acute GVHD after administration of brentuximab vedotin [ Time Frame: Up to day 28 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 37
Study Start Date: September 2012
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: pharmacological studies

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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01616680

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Merav Bar     206-667-4545        
Principal Investigator: Merav Bar            
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
National Cancer Institute (NCI)
Investigators
Principal Investigator: Merav Bar Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT01616680     History of Changes
Other Study ID Numbers: 2589.00, NCI-2012-00921
Study First Received: June 7, 2012
Last Updated: March 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Antibodies, Monoclonal
Immunoconjugates
 Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013