Maraviroc as GVHD Prophylaxis in Transplant Recipients

Study Overview
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Brief Summary
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The purpose is to determine if the addition of Maraviroc to a standard transplant regimen will reduce the incidence of graft versus host disease in children and young adults after a stem cell transplant.

Detailed Description
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In the first stage, drug levels will be obtained to establish appropriate dosing. In the second stage of the study the investigators will study the effects of using Maraviroc in these patients.

Official Title
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Maraviroc as Graft Versus Host Disease Prophylaxis in Pediatric and Adult Stem Cell Transplant Recipients

Conditions
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Diagnoses That Require Stem Cell Transplant, Graft Versus Host Disease (GVHD)

Intervention / Treatment
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* Drug: Maraviroc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 5 years and </= 40 years All diagnoses Peripheral blood stem cells, marrow or cord blood All conditioning regimens Patient must be planned to receive a calcineurin inhibitor (cyclosporine or tacrolimus) together with steroid, methotrexate or mycophenolate mofetil as GVHD prophylaxis. Exclusion Criteria: Documented anaphylaxis to Maraviroc Ex vivo T-cell (type of white blood cell) depleted grafts Abnormal Alanine Aminotransferase (ALT) (>/=10X ULN) on day -3. (Assessed at study enrollment and confirmed again prior to the first dose of maraviroc.)

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 40 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maraviroc<br>Maraviroc administration will start on day -3 and will end on day +30 after stell cell transplant, making the total number of days of drug administration 34 days. Maraviroc will be administered twice daily orally or via enteral tube. Dosing of Maraviroc will be based on body surface area (starting with 100mg twice a day for BSA of 0.2 and up to 300mg twice a day for BSA greater than 1.73). | Drug: Maraviroc<br> <br> * Other names: Selzentry;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Maraviroc | The ability to administer twice daily oral maraviroc in children and adults undergoing stem cell transplant in addition to routine standard graft versus host disease prophylaxis. | Up to day +100 | 
| GVHD Incidence | Incidence of GVHD by day+100 | By day +100 | 
| Area Under The Concentration-Time Curve (AUC) of Maraviroc | pK target >100ng/ml at day zero at the following time points : before the dose and 1, 2, 4, 6, 8, and 12 hours after maraviroc administration | Day 0 | 
| Incidence of Visceral GVHD | determine the number of patients who develop visceral GVHD by day+100 | day+100 | 
| Area Under The Concentration-Time Curve (AUC) of Maraviroc | pK target >100ng/ml at day 10 at the following time points : before the dose and 1, 2, 4, 6, 8, and 12 hours after maraviroc administration | Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival for patients who were enrolled and received maraviroc | By day +100 | 
| Graft Failure | Failure to engraft and loss of graft. | By day +100 | 
| Primary Disease Relapse |  | By day +100 | 
| Toxicities | Incidence of toxicities due to drug | Up to day +100 | 
| Infectious Complications | Infections complications which include asymptomatic viremias for EBV, Adenovirus, CMV, and/or viral disease, bacterial and fungal infections as documented by blood cultures. | Up to day +100 | 
| Time to Neutrophil | Neutrophil engraftment is defined as the first of three consecutive measurements of ANC>500mcL over 3 or more days. | Up to day +100 | 
| Time to Platelet Engraftment | Time to achieve platelets count of 20,000 without transfusions | days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cell transplant, GVHD prevention