Efalizumab in Treating Patients With Graft-Versus-Host Disease of the Skin That Did Not Respond to Previous Steroids

NCT00489216 | Terminated Results DMC

• 1 other identifier: LCCC 0605
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Efalizumab may be an effective treatment for graft-versus-host disease of the skin caused by a donor stem cell transplant. PURPOSE: This clinical trial is studying the side effects and how well efalizumab works in treating patients with graft-versus-host disease of the skin that did not respond to previous steroids.

Conditions

Graft Versus Host Disease

Keywords

Graft Versus Host Disease; GVHD; Efalizumab; Raptiva; Steroid; Refractory; Skin; Liver; Lineberger; University of North Carolina

Outcome Measures

Primary Outcomes (3)

• Number of Subjects Experiencing Adverse Events

  The primary objective of this exploratory study is to evaluate the general tolerability of efalizumab in patients suffering from steroid refractory GVHD Subjects will be evaluated for drug toxicity each visit. Toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) common criteria.

  120 days

• Degree of Skin Involvement by GVHD Using Two Digital Photography Techniques.

  Estimate of the percentage of body surface area involved by GVHD using two digital photography techniques and computerized image analyses: 1. Digital photography and body surface area calculations: A total of 12 digital photographs were obtained from different body regions using systematic digital imaging and computerized image analysis. 2. Body surface area calculations: Using National Institutes of Health image software, each body region will be manually traced and the total area of the traced area determined. Using a similar technique, each part of the region that is involved by a GVHD rash will also be traced and its area measured. The areas involved by rash will then be summed, and finally divided by the total area of the region. In so doing, the percentage of each region that is involved by GVHD will be determined.

  120 days

• Exploratory Assessment of the Staining of Cutaneous Tissues for LFA-1, ICAM-1, CD4, CD8, and Possibly CD20

  Numerical scoring system for both LFA-1 and ICAM-1 expression which could then be used in a larger phase II trial to correlate clinical response rates to pathological findings.

  57 days

Secondary Outcomes (3)

• Overall Complete Response Rate

  57 days

• Complete Cutaneous Response Rate

  On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab

• Overall Hepatic Response Rate

  On study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab

Study Arms (1)

Efalizumab

EXPERIMENTAL

All patients on study will receive a total of 8 injections of efalizumab

Biological: efalizumab

Interventions

efalizumab BIOLOGICAL

Efalizumab will be administered as a subcutaneous injection once a week for 8 weeks (total of 8 doses). First efalizumab injection will be dosed at 0.7mg/kg. Subsequent weekly injections given on days 8-50 will be dosed at 1mg/kg

Also known as: Raptiva

Efalizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Skin disease
• Patients must demonstrate evidence of an erythematous maculopapular rash which is felt to be clinically consistent with graft-versus-host disease. Patients must undergo skin biopsy prior to enrollment. Because the pathological findings of GVHD may be equivocal (6) a biopsy which is felt to be consistent with GVHD will be considered adequate.
• Consider sclerodermatous skin changes may be present but will not by themselves adequate for enrollment. Patients must exhibit signs of an active inflammatory rash.
• Liver disease
• Although hepatic involvement is not required for study participation, patients with concomitant GVHD of the liver are encouraged to enroll. All patients with hepatic GVHD must also demonstrate cutaneous disease. Patients with liver dysfunction are encouraged but not required to undergo hepatic biopsy in order to document that liver injury is the result of GVHD. Patients with a pretreatment serum bilirubin ≥ 2.0 mg/dL and biopsy-confirmed cutaneous GVHD will be assumed to demonstrate hepatic GVHD if no other cause for the liver function test (LFT) elevation can be identified.
• Age ≥ 18 years
• Patients must be ≥ 30 days removed from allogeneic hematopoietic stem cell transplant in order to allow for engraftment. Patients receiving peripheral blood stem cells and/or bone marrow will be eligible, regardless of the degree of human leukocyte antigen (HLA) matching.
• Steroid refractory disease
• All patients must demonstrate evidence of steroid refractory graft-versus host disease of the skin or liver. In an effort to conform to a standard definition of steroid refractory disease, we will base our criteria on those described in a large intergroup trial examining the effectiveness of pentostatin for steroid refractory chronic GVHD (31). Because the present study, however, is designed to include patients with both acute and chronic GVHD based on traditional disease classification criteria, the required time intervals necessary to define steroid-refractoriness have been shortened. Patients will be considered steroid refractory if any one of the following conditions is met:
• Worsening skin or liver disease despite 1 week on the equivalent of 1mg/kg of methylprednisolone
• Failure to achieve a 50% reduction in the body surface area involved by GVHD or a 50% reduction in the total serum bilirubin after 4 weeks on the equivalent of at least 0.5 mg/kg of methylprednisolone
• Requirement of ≥ the equivalent of 0.5mg/kg of methylprednisolone to maintain a response after 8 weeks of steroid therapy
• Patients with progression of cutaneous or hepatic GVHD after a prior history of treatment with at least 8 weeks of corticosteroids now requiring the reintroduction of corticosteroids (\> the equivalent of 10mg/day of methylprednisolone)
• Patients with GVHD not improving or progressing on alternative immunosuppressive agents will be eligible if steroid refractoriness has been established previously
• Required initial laboratory values:

You may not qualify if:

• Non-pregnant and non-nursing
• Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential must agree to use an effective means of birth control.
• No HIV infection
• PRIOR CONCURRENT THERAPY:
• See Disease Characteristics
• At least 2 terminal half-lives since prior and no concurrent infliximab, daclizumab, etanercept, rituximab, antithymocyte globulin (ATG), or denileukin diftitox

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

efalizumab

Condition Hierarchy (Ancestors)

Immune System Diseases

Limitations and Caveats

The study was terminated early due to funding withdrawal/insufficient accrual limiting the data to be analyzed.

Results Point of Contact

• Title: Robin V. Johnson
• Organization: UNC Lineberger Comprehensive Cancer Center

Robin_V_Johnson@med.unc.edu

919-966-1125

Study Officials

• Thomas C. Shea, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 21, 2007
• Study Start: December 1, 2006
• Primary Completion: June 1, 2008
• Study Completion: October 1, 2008
• Last Updated: May 23, 2017
• Results First Posted: April 6, 2017

Record last verified: 2017-04

Locations

US (1)