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

Purpose

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.

Condition	Intervention
Graft Versus Host Disease	Biological: efalizumab

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Supportive Care
Official Title:	Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:

Number of subjects experiencing adverse events [ Time Frame: 120 days ] [ Designated as safety issue: Yes ]
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 NCTCAE common criteria.

Secondary Outcome Measures:

Feasibility of digital imaging [ Time Frame: 120 days ] [ Designated as safety issue: No ]
To study the feasibility of digital imaging to objectively quantify cutaneous GVHD.
Feasibility of serial skin biopsies [ Time Frame: 57 days ] [ Designated as safety issue: No ]
To evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab therapy in patients with cutaneous GVHD.
Overall complete response rate [ Time Frame: 57 days ] [ Designated as safety issue: No ]
To assess the overall complete response rate on study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab.

Enrollment:	2
Study Start Date:	May 2007
Study Completion Date:	October 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Efalizumab All patients on study will receive a total of 8 injections of efalizumab	Biological: efalizumab 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 Other Name: Raptiva

Detailed Description:

OBJECTIVES:

Primary

Assess the general safety of efalizumab in patients with cutaneous graft-vs-host disease (GVHD).
Study the feasibility of digital imaging to objectively quantify cutaneous GVHD.
Evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab in patients with cutaneous GVHD.

Secondary

Assess the overall complete response rate in patients treated with this drug.
Assess the overall cutaneous response rate (complete cutaneous response rate and partial cutaneous response rate) in patients treated with this drug.
Assess the overall hepatic response rate (complete hepatic response rate and partial hepatic response rate) in patients treated with this drug.
Assess the duration of any responses observed.
Assess the effect of this drug on overall patient survival.
Use the preliminary efficacy and toxicity data collected in this small exploratory study to decide on the appropriateness of a larger, subsequent phase II trial to more formally assess toxicity and efficacy of this drug in this patient population.
Collect pharmacokinetic data on this drug in these patients.

OUTLINE: Patients receive efalizumab subcutaneously once weekly for 8 weeks (total of 8 doses).

Digital photographs of body regions are taken for determination of disease involved body surface area. Skin biopsies are obtained before and after treatment and analyzed for LFA-1, ICAM-1, CD4, CD8, and possibly CD20 by immunohistochemistry.

After completion of study therapy, patients are followed at 1 and 9 weeks.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of acute or chronic cutaneous graft-versus-host disease (GVHD), as evidenced by an erythematous maculopapular rash which is felt to be clinically consistent with GVHD
- Pathologic findings from skin biopsy consistent with GVHD
- Sclerodermatous skin changes may be present but will not by themselves be considered adequate for study enrollment
Patients with concurrent hepatic GVHD are eligible
- 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 bilirubin elevation can be identified
Underwent allogeneic hematopoietic stem cell transplantation (peripheral blood stem cells and/or bone marrow, regardless of the degree of HLA matching) ≥ 30 days prior to study enrollment
Steroid refractory disease, defined by 1 of the following criteria:
- Worsening skin or liver disease despite 1 week of treatment with the equivalent of 1 mg/kg of methylprednisolone
- Failed 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 of treatment with the equivalent of at least 0.5 mg/kg of methylprednisolone
- Requires the equivalent of at least 0.5 mg/kg of methylprednisolone to maintain a response after 8 weeks of steroid therapy
- 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 greater than 10 mg/day of methylprednisolone)
- Not improving or progressing on alternative immunosuppressive agents after prior steroid refractoriness had been established

PATIENT CHARACTERISTICS:

Not pregnant or nursing
Fertile patients must use effective contraception
Absolute neutrophil count (ANC) > 1,000/μL
Platelet count ≥ 20,000/μL
Serum creatinine ≤ 3.0 mg/dL
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489216

Locations

United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295

Sponsors and Collaborators

UNC Lineberger Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Thomas C. Shea, MD

UNC Lineberger Comprehensive Cancer Center

More Information

Additional Information:

Lineberger Comprehensive Cancer Center website This link exits the ClinicalTrials.gov site

National Cancer Institute (NCI) This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00489216 History of Changes
Other Study ID Numbers:	LCCC 0605, CDR0000550090
Study First Received:	June 20, 2007
Last Updated:	February 1, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:

Graft Versus Host Disease
GVHD
Efalizumab
Raptiva
Steroid

Refractory
Skin
Liver
Lineberger
University of North Carolina

Additional relevant MeSH terms:

Graft vs Host Disease
Immune System Diseases
Antibodies, Monoclonal

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013