Maraviroc-Based GVHD Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Transplantation

Phase 2

• Conditions: Graft-versus-host Disease; Hematopoietic Stem Cell Transplantation
• Interventions: Drug: Maraviroc; Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation); Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation); Drug: Methotrexate

• Registration Number: NCT02799888
• Lead Sponsor: Affiliated Hospital to Academy of Military Medical Sciences

Brief Summary

HLA-mismatched unrelated donor (MMUD) and HLA-haploidentical donor (Haplo Donor) hematopoietic stem cell transplantation (HSCT) is associated with increased graft-versus-host-disease (GVHD) and impaired survival. The chemokine receptor 5 (CCR5) antagonist maraviroc has immunomodulatory properties potentially beneficial for GVHD control as it can blockade lymphocyte chemotaxis without impairing T-cell function. The aim of this study is to evaluate the safety and efficacy of maraviroc combined with standard graft-versus-host-disease prophylaxis in patients with hematologic malignancies after allogeneic stem cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors. Based on the results of our previously small sample study with maraviroc combined with cyclosporine/tacrolimus and methotrexate for prophylaxis of GVHD, the investigators plan to perform the clinical trail.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04
• Status Verified: 2016-06
• Study First Submitted: 2016-06-03
• Study First Submitted QC: 2016-06-09
• Last Update Submitted: 2016-06-09
• Study First Posted: 2016-06-15
• Last Update Posted: 2016-06-15
• Primary Completion: 2016-12
• Study Completion: 2017-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Age 12-65 years (patient is older than 12.0 and less than 66.0 years old)
2. Patients with acute leukemia, myelodysplastic syndrome or lymphoma who scheduled to undergo allogeneic stem-cell transplantation from HLA-Unrelated or HLA-Mismatched Related donors
3. Renal function: estimated creatinine clearance greater than 40 mL/minute (using the Cockcroft-Gault formula and actual body weight)
4. Hepatic function: Baseline direct bilirubin, alanine aminotransferase (ALT) lower than three times the upper limit of normal
5. Pulmonary disease: forced vital capacity (FVC) or forced expiratory volume at one second (FEV1) > 40% predicted
6. Cardiac ejection fraction > 40%
7. Signed informed consent

Exclusion Criteria

1. Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant
2. Prior allogeneic transplant
3. Karnofsky Performance Score < 70%
4. Patients who are not undergoing standard GVHD prophylaxis with cyclosporine/tacrolimus and methotrexate
5. Patients with uncontrolled bacterial, viral or fungal infections
6. Patients receiving other investigational drugs for GVHD

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Maraviroc + standard GVHD prophylaxis	Cyclosporine (in HLA-Unrelated Donor Transplantation)	Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
Maraviroc + standard GVHD prophylaxis	Tacrolimus (in HLA-Mismatched Related Donor Transplantation)	Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
Maraviroc + standard GVHD prophylaxis	Maraviroc	Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.
Maraviroc + standard GVHD prophylaxis	Methotrexate	Maraviroc administration (in addition to the standard prophylaxis therapy of cyclosporine/tacrolimus and methotrexate) will start on day -2 and will end on day +30 after stem cell transplant, making the total number of days of drug administration 33 days. Maraviroc will be administered 300mg twice daily orally.

Primary Outcome Measures

Name	Time	Method
Incidence of Acute GVHD Grades II-IV	1 Year

Secondary Outcome Measures

Name	Time	Method
Incidence of Grade 2 and 3 Infections	1 Year
Overall Survival	1 Year
Incidence of Acute GVHD Grades III-IV	By day +100 post-HSCT
Incidence of Transplant-Related Mortality	By day +100 post-HSCT
Frequency of Grade 3 or Greater Toxicities	Up to day +100 post-HSCT
Disease Relapse or Progression	1 Year
Incidence of Chronic GVHD	1 Year
Hematologic Recovery (Neutrophils and Platelets)	Up to day +100 post-HSCT

Trial Locations

Locations (1)

Department of Hematopoietic Stem Cell Transplantation; 🇨🇳 Beijing, Beijing, China