Maraviroc in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation

Safety and Efficacy of Maraviroc, a CCR5-inhibitor in Prophylaxis of Graft-Versus-Host Disease in Patients Undergoing Non-Myeloablative Allogeneic Stem-Cell Transplantation

This study investigates the effectiveness and safety of Maraviroc (an oral medication given twice daily given in addition to the standard GVHD prophylaxis) in preventing Graft versus Host Disease (GVHD) in patients undergoing non-myeloablative allogeneic stem-cell transplantation (SCT). Subjects will receive Maraviroc bid (in addition to standard GVHD prophylaxis) beginning after the last dose of the chemotherapy conditioning regimen until day 30 after stem-cell infusion.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation; Graft-versus-host Disease
• Intervention / Treatment: Drug: Maraviroc 150 MG; Drug: Maraviroc 300 mg; Drug: Maraviroc 300 mg Phase II

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 1

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:

• patients scheduled to undergo non-myeloablative allogeneic stem-cell transplantation.

• meet institutional eligibility criteria for allogeneic SCT. Significant criteria are:

  • Renal function: Serum creatinine <2; or calculated creatinine clearance > 40 mL/min/1.72m2;
  • Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times the upper limit of normal;
  • Pulmonary disease: FVC or FEV1 > 40% predicted; Cardiac ejection fraction > 40%.

Exclusion Criteria:

• Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
• Patients who are not undergoing standard non-myeloablative SCT with Flu/Bu conditioning and Tax/MTX GVHD prophylaxis
• Patients with uncontrolled bacterial, viral or fungal infections
• Patients who take strong inducers or inhibitors of the CYP450A4
• Patients receiving other investigational drugs for GVHD
• Women who are pregnant, plan to become pregnant or are breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: 150mg Maraviroc; 150mg twice daily	Drug: Maraviroc 150 MG; Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.; Other Names: CCR5 Blockade
Experimental: Phase 1: 300mg Maraviroc; 300mg twice daily	Drug: Maraviroc 300 mg; Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.; Other Names: CCR5 Blockade
Experimental: Phase 2: 300mg Maraviroc; 300mg twice daily	Drug: Maraviroc 300 mg Phase II; Maraviroc b.i.d. (in addition to the standard prophylaxis therapy of tacrolimus and methotrexate) beginning after last dose of chemotherapy conditioning regimen until day 30 after stem-cell infusion.; Other Names: CCR5 Blockade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Maraviroc	number of Adverse Events following exposure to Maraviroc	1 year
Efficacy of Maraviroc	Efficacy is measured by number of participants progressing to acute GVHD. If acute GVHD is noted in a participant following exposure to study drug, then efficacy was not achieved. If no GVHD was noted following exposure, then efficacy was achieved in that participant	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Profile of Maraviroc in Patients Undergoing Nonmyeloablative Allogeneic SCT	Plasma maraviroc levels were measured in the blood with a target level of 100 ng per milliliter. Blood was drawn on Day 0 and Day 10-12 at pre-dose, 1, 2, 3, 4, 6, and 12 hours post-dose. Data was analyzed looking at the number of patients to achieve the target of 100 ng per milliliter at any time point.	pre-dose, 1,2,3,4,6,12 hours post-dose
Number of Patients Treated With Maraviroc During SCT That Develop Chronic GVHD	count of how many patients treated with Maraviroc during SCT go on to develop chronic GVHD in 1 year	1 year
Rate of Early Mortality After Transplant	Number of participants who died without relapse within 1 year of SCT	1 year
Number of Participants Who Relapsed During Study Period	Number of participants who received Maraviroc during SCT who relapsed within 1 year and 11 months. This was based on a diagnosis made by their physician that their primary cancer had returned.	1 year and 11 months

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Investigators: Principal Investigator: David Porter, MD, University of Pennsylvania

Publications and helpful links

General Publications

• Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, Goldstein SC, Stadtmauer EA, Smith J, Bailey S, Mick R, Heitjan DF, Emerson SG, Hoxie JA, Vonderheide RH, Porter DL. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med. 2012 Jul 12;367(2):135-45. doi: 10.1056/NEJMoa1201248.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2009
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: July 23, 2009
• First Submitted That Met QC Criteria: July 28, 2009
• First Posted (Estimate): July 29, 2009

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: GVHD; Hematopoietic stem cell transplantation; Maraviroc; Graft-versus-host disease; non-myeloablative allogeneic stem-cell transplantation
• 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: UPCC 04708