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

Sponsor

Affiliated Hospital to Academy of Military Medical Sciences (Other)

Overall Status

Unknown status

CT.gov ID

NCT02799888

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease Hematopoietic Stem Cell Transplantation	Drug: Maraviroc Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation) Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation) Drug: Methotrexate	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Safety and Efficacy of Maraviroc-Based Graft-Versus-Host-Disease Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Donor Transplantation

Study Start Date :

Apr 1, 2014

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maraviroc + standard GVHD prophylaxis 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.	Drug: Maraviroc Maraviroc will be administered 300mg twice daily and start on day -2 end on day +30 after stem cell transplant for 33 days. Other Names: Selzentry Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation) Cyclosporine will be given intravenously at a dose of 2-3 mg/kg starting Day -1. Subsequent dosing will be based on blood levels. Patients were advanced to oral cyclosporine once they could tolerate. The dose should be adjusted accordingly to maintain a suggested target serum level of 150-250 ng/mL. In the absence of aGVHD, the oral cyclosporine dose was reduced by approximately 5% weekly, beginning on or near day 100, and therapy was usually discontinued by Day 180 after transplantation or relapse. Other Names: Sandimmune Gengraf Neoral Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation) Tacrolimus will be given orally at a dose of 0.05 mg/kg twince a day or intravenously at a dose of 0.03 mg/kg starting Day -3. Subsequent dosing should be adjusted accordingly to maintain a suggested target serum level of 5-10 ng/mL. Tacrolimus taper can be initiated at a minimum of 100 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD. Other Names: Prograf® FK506 Drug: Methotrexate Methotrexate will be administered intravenously at a dose of 15 mg/m^2 on day +1, and 10 mg/m^2 on day +3, +6 and +11 after HSC transplantation.at the doses of 15 mg/m^2 IV bolus on Day +1, and 10 mg/m^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +11 dose of methotrexate will be not given to those patients who fail to reach white blood cell count (WBC) of more than 1.0×10^9/L. Other Names: MTX

Arm

Intervention/Treatment

Experimental: Maraviroc + standard GVHD prophylaxis

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.

Drug: Maraviroc

Maraviroc will be administered 300mg twice daily and start on day -2 end on day +30 after stem cell transplant for 33 days.

Other Names:

Selzentry

Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation)

Cyclosporine will be given intravenously at a dose of 2-3 mg/kg starting Day -1. Subsequent dosing will be based on blood levels. Patients were advanced to oral cyclosporine once they could tolerate. The dose should be adjusted accordingly to maintain a suggested target serum level of 150-250 ng/mL. In the absence of aGVHD, the oral cyclosporine dose was reduced by approximately 5% weekly, beginning on or near day 100, and therapy was usually discontinued by Day 180 after transplantation or relapse.

Other Names:

Sandimmune

Gengraf

Neoral

Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation)

Tacrolimus will be given orally at a dose of 0.05 mg/kg twince a day or intravenously at a dose of 0.03 mg/kg starting Day -3. Subsequent dosing should be adjusted accordingly to maintain a suggested target serum level of 5-10 ng/mL. Tacrolimus taper can be initiated at a minimum of 100 days post HSCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices but patients should be off tacrolimus by Day 180 post HSCT if there is no evidence of active GVHD.

Other Names:

Prograf®

FK506

Drug: Methotrexate

Methotrexate will be administered intravenously at a dose of 15 mg/m^2 on day +1, and 10 mg/m^2 on day +3, +6 and +11 after HSC transplantation.at the doses of 15 mg/m^2 IV bolus on Day +1, and 10 mg/m^2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. The Day +11 dose of methotrexate will be not given to those patients who fail to reach white blood cell count (WBC) of more than 1.0×10^9/L.

Other Names:

MTX

Outcome Measures

Primary Outcome Measures

Incidence of Acute GVHD Grades II-IV [1 Year]

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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