Maraviroc as GVHD Prophylaxis in Transplant Recipients

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

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.

Study Overview

• Status: Terminated
• Conditions: Graft Versus Host Disease (GVHD); Diagnoses That Require Stem Cell Transplant
• Intervention / Treatment: Drug: Maraviroc

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 40 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Maraviroc; 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; Other Names: Selzentry

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Pooja Khandelwal, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: June 13, 2014
• First Submitted That Met QC Criteria: June 17, 2014
• First Posted (Estimate): June 19, 2014

Study Record Updates

• Last Update Posted (Actual): March 10, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: stem cell transplant; GVHD prevention
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: 2014-1221