Study of MEDI 507 in the Treatment of Pediatric Patients

Study Overview
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Brief Summary
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To assess the safety of escalating dose levels of MEDI-507 in pediatric stem cell and bone marrow allograft recipients who have at least Grade II GvHD.

Detailed Description
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This is a Phase I, open-label dose escalation trial of MEDI-507 in pediatric SCT and BMT recipients with at least Grade II acute GvHD. All patients will receive steroid therapy and MEDI-507 for treatment of GvHD

Official Title
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Phase I Study of MEDI 507 in the Treatment of Pediatric Patients With at Least Grade II Acute Graft-Versus-Host Disease (GvHD)

Conditions
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Graft Versus Host Disease

Intervention / Treatment
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* Drug: MEDI-507
* Drug: MEDI-507
* Drug: MEDI-507


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Allogeneic BMT or SCT recipients Acute GvHD of at least Grade II severity Age 2 to 17 years Evidence of engraftment (ANC over 500 cells/mm3 on two consecutive days within seven days before study entry) Receipt of GvHD prophylaxis regimen including methotrexate, tacrolimus or cyclosporine Receipt of at least 2 mg/kg of methylprednisolone (or equivalent corticosteroid) between eight and 24 hours prior to the first MEDI-507 dose for GvHD treatment Both males and females are eligible, but sexually active females at risk of pregnancy of childbearing potential must agree to use an effective method of avoiding pregnancy (which includes oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) beginning 30 days before the first study infusion and continuing through 60 days after the final study infusion. Exclusion Criteria: Treatment of acute GvHD with methylprednisolone (or equivalent corticosteroid) at a total dose exceeding 14 mg/kg (or equivalent) over a seven day period (for example, 2 mg/kg/day for seven days) Previous receipt of MEDI 507 Previous treatment with any anti-T cell monoclonal antibodies, such as OKT3, daclizumab (Zenapax), or basiliximab (Simulect) Treatment with anti-thymocyte globulin (ATG, ATGAM or others) within 14 days More than one allogeneic bone marrow or hematopoietic stem cell allograft 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) or current participation in a research protocol in which an investigational agent was administered Any of the following clinical settings or diagnoses: documented or presumed significant active infection pregnancy or nursing mother evidence of infection with HIV-1, hepatitis B or C virus hemodialysis or chronic peritoneal dialysis use of a ventilator chronic GvHD active veno-occlusive disease of the liver moribund patient

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MEDI-507 | Drug: MEDI-507<br>* 0.012 mg/kg given intravenously on Study Days 0, 3, 6 and 9<br>|
| Experimental: 2<br>MEDI-507 | Drug: MEDI-507<br>* 0.04 mg/kg given intravenously on Study Days 0, 3, 6 and 9<br>|
| Experimental: 3<br>MEDI-507 | Drug: MEDI-507<br>* 0.12 mg/kg given intravenously on Study Days 0, 3, 6 and 9<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessment of escalating dose levels of MEDI-507 in pediatric stell scell (SCT) and bone marrow (BMT) allograft recipients who have at least Grade II Graft-versus-Host Disease (GvHD). |  | Through Study Day 44 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the serum concentrations and pharmacokinetics (PK) of MEDI 507 and pharmacodynamic effects of MEDI-507 on the absolute lymphocyte count and dynamics of lymphocyte phenotypes. |  | Through Study Day 364 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute GvHD of at least Grade II severity