Study of MEDI-507 in With Steroid-Resistant Acute Graft-Versus-Host Disease

Phase I Study of MEDI-507 in the Treatment of Adult Patients With at Least Grade II Steroid-Resistant Acute Graft-Versus-Host Disease

A clinical trial to assess safety and two regimens of (MEDI-507) a drug given to stem cell and bone marrow recipients who have a mid-grade acute Graft-versus-Host Disease.

Study Overview

• Status: Completed
• Conditions: Cancer; Graft-Versus-Host Disease
• Intervention / Treatment: Drug: MEDI-507; Drug: MEDI-507

Detailed Description

To assess the safety of two regimens of MEDI-507 administered to stem cell and bone marrow allograft recipients who have at least grade II acute GVHD and who have not achieved a satisfactory response to at least three days of corticosteroid therapy (2 mg/kg/day of methylprednisolone or its equivalent).

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hospital
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University Hospital-University of Oklahoma
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital - Western Pennsylvania Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Cancer Institute at Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Allogeneic bone marrow or hematopoietic stem cell graft recipients
• Acute GVHD of at least grade II severity
• Failure of GVHD to improve on at least 2 mg/kg/day of methylprednisolone or prednisone for at least three days or recurrence of acute GVHD as corticosteroids are tapered from initial treatment of the initial episode of GVHD
• Evidence of engraftment (ANC over 1000 cells/mm3)
• Histologic evidence of GVHD from biopsy performed during the current episode
• Received GVHD prophylaxis of methotrexate, tacrolimus or cyclosporine
• Age at least 18 years
• Body weight under 130 kg
• Both males and females are eligible but females of childbearing potential will use an accepted method of avoiding pregnancy for at least 60 days after the end of treatment (which includes oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or a sterile sexual partner)

Exclusion Criteria:

• Previous receipt of MEDI-507
• Clinical or histologic manifestation of chronic GVHD
• Previous treatment with any anti-T-cell antibodies such as OKT®3 or daclizumab (Zenapax®)
• Receipt of antithymocyte globulin (ATGAM® or other ATG) since the day of transplant
• More than one allogeneic bone marrow or hematopoietic stem cell allograft
• Moribund and unlikely (in the opinion of the investigator) to survive 15 days
• Use of other investigational agents within 30 days (this does not include the use of licensed agents for indications not listed in the package insert)
• Any of the following clinical settings or diagnoses:

Ø documented or presumed significant active infection Ø pregnancy or nursing mother Ø evidence of infection with HIV-1, hepatitis B or C virus Ø hemodialysis or chronic peritoneal dialysis Ø use of a ventilator

• Histologically confirmed veno-occlusive disease of the liver
• Ascites on physical examination (this does not include small amounts of ascitic fluid detected only on ultrasound)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; MEDI-507	Drug: MEDI-507; 0.12 mg/kg of MEDI-507 given every third day for 4 doses followed by doses of normal saline on Days 16, 23, 30, and 37.; Drug: MEDI-507; 0.12 mg/kg of MEDI-507 given every third day for 4 doses followed by doses of MEDI-507 on Days 16, 23, 30, and 37.
Experimental: 2; MEDI-507	Drug: MEDI-507; 0.12 mg/kg of MEDI-507 given every third day for 4 doses followed by doses of normal saline on Days 16, 23, 30, and 37.; Drug: MEDI-507; 0.12 mg/kg of MEDI-507 given every third day for 4 doses followed by doses of MEDI-507 on Days 16, 23, 30, and 37.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety was assessed by the direct observation of patients, medical history, and clinical laboratory evaluation to determine the incidence of patients experiencing AEs.	Day 0-60

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics, Lymphocyte Phenotype and CD2 Receptor Occupancy Pharmacodynamics	Study Days 12 and 44

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: J. Bruce McClain, M.D., MedImmune LLC

Study record dates

Study Major Dates

• Study Start: May 1, 1998
• Primary Completion (Actual): November 1, 1998
• Study Completion (Actual): December 1, 1998

Study Registration Dates

• First Submitted: December 10, 2008
• First Submitted That Met QC Criteria: December 10, 2008
• First Posted (Estimate): December 11, 2008

Study Record Updates

• Last Update Posted (Estimate): December 11, 2008
• Last Update Submitted That Met QC Criteria: December 10, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: MI-CP042