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

Graft Versus Host Disease Clinical Trial

— NRR  

Official title:

Weekly Subcutaneous Efalizumab for the Treatment of Steroid Refractory Graft-Versus-Host Disease of the Skin and Liver

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00489216
• Other study ID #: LCCC 0605
• Secondary ID: CDR0000550090
• Status: Terminated
• Phase: N/A
• First received: June 20, 2007
• Last updated: January 20, 2016
• Start date: December 2006
• Est. completion date: October 2008

Study information

• Verified date: January 2016
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: October 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease

Intervention

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

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 NCTCAE common criteria.	120 days	Yes
Secondary	Feasibility of digital imaging	To study the feasibility of digital imaging to objectively quantify cutaneous GVHD.	120 days	No
Secondary	Feasibility of serial skin biopsies	To evaluate the feasibility of serial skin biopsies to monitor disease response to efalizumab therapy in patients with cutaneous GVHD.	57 days	No
Secondary	Overall complete response rate	To assess the overall complete response rate on study days 29 and 57 after 4 and 8 doses of weekly subcutaneous efalizumab.	57 days	No

External Links

•   National Cancer Institute (NCI)