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

Study Overview
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Brief Summary
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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.

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

Conditions
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Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation

Intervention / Treatment
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* Drug: Maraviroc 150 MG
* Drug: Maraviroc 300 mg
* Drug: Maraviroc 300 mg Phase II


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: 150mg Maraviroc<br>150mg twice daily | Drug: Maraviroc 150 MG<br>* 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.<br>* Other names: CCR5 Blockade;|
| Experimental: Phase 1: 300mg Maraviroc<br>300mg twice daily | Drug: Maraviroc 300 mg<br>* 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.<br>* Other names: CCR5 Blockade;|
| Experimental: Phase 2: 300mg Maraviroc<br>300mg twice daily | Drug: Maraviroc 300 mg Phase II<br>* 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.<br>* Other names: CCR5 Blockade;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-myeloablative allogeneic stem-cell transplantation, Hematopoietic stem cell transplantation, Graft-versus-host disease, GVHD, Maraviroc