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

Primary Purpose

Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation

Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Maraviroc
Cyclosporine (in HLA-Unrelated Donor Transplantation)
Tacrolimus (in HLA-Mismatched Related Donor Transplantation)
Methotrexate
Sponsored by
Affiliated Hospital to Academy of Military Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Graft-versus-host Disease focused on measuring Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation, Acute Leukemia, Myelodysplastic syndrome, Lymphoma

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Hematopoietic Stem Cell TransplantationRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Maraviroc + standard GVHD prophylaxis

Arm Description

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.

Outcomes

Primary Outcome Measures

Incidence of Acute GVHD Grades II-IV

Secondary Outcome Measures

Incidence of Acute GVHD Grades III-IV
Incidence of Chronic GVHD
Hematologic Recovery (Neutrophils and Platelets)
Disease Relapse or Progression
Incidence of Transplant-Related Mortality
Frequency of Grade 3 or Greater Toxicities
Incidence of Grade 2 and 3 Infections
Overall Survival

Full Information

First Posted
June 3, 2016
Last Updated
June 9, 2016
Sponsor
Affiliated Hospital to Academy of Military Medical Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02799888
Brief Title
Maraviroc-Based GVHD Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Transplantation
Official Title
Safety and Efficacy of Maraviroc-Based Graft-Versus-Host-Disease Prophylaxis in HLA-Unrelated and HLA-Mismatched Related Donor Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
April 2014 (undefined)
Primary Completion Date
December 2016 (Anticipated)
Study Completion Date
April 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Affiliated Hospital to Academy of Military Medical Sciences

4. Oversight

Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation
Keywords
Graft-versus-host Disease, Hematopoietic Stem Cell Transplantation, Acute Leukemia, Myelodysplastic syndrome, Lymphoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Maraviroc + standard GVHD prophylaxis
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Other Intervention Name(s)
Selzentry
Intervention Description
Maraviroc will be administered 300mg twice daily and start on day -2 end on day +30 after stem cell transplant for 33 days.
Intervention Type
Drug
Intervention Name(s)
Cyclosporine (in HLA-Unrelated Donor Transplantation)
Other Intervention Name(s)
Sandimmune, Gengraf, Neoral
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus (in HLA-Mismatched Related Donor Transplantation)
Other Intervention Name(s)
Prograf®, FK506
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
MTX
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of Acute GVHD Grades II-IV
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Incidence of Acute GVHD Grades III-IV
Time Frame
By day +100 post-HSCT
Title
Incidence of Chronic GVHD
Time Frame
1 Year
Title
Hematologic Recovery (Neutrophils and Platelets)
Time Frame
Up to day +100 post-HSCT
Title
Disease Relapse or Progression
Time Frame
1 Year
Title
Incidence of Transplant-Related Mortality
Time Frame
By day +100 post-HSCT
Title
Frequency of Grade 3 or Greater Toxicities
Time Frame
Up to day +100 post-HSCT
Title
Incidence of Grade 2 and 3 Infections
Time Frame
1 Year
Title
Overall Survival
Time Frame
1 Year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongmei Ning, M.D., Ph.D.
Phone
+86 10 66947405
Email
ninghongmei72@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yongfeng Su, M.D., Ph.D.
Phone
+86 10 66947122
Email
suyongfeng199705@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hu Chen, M.D., Ph.D.
Organizational Affiliation
Affiliated Hospital to Academy of Military Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematopoietic Stem Cell Transplantation
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100071
Country
China
Individual Site Status
Recruiting

12. IPD Sharing Statement

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

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