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

Hematopoietic Stem Cell Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02799888
• Other study ID #: 307-maraviroc-001
• Status: Recruiting
• Phase: Phase 2
• First received: June 3, 2016
• Last updated: June 9, 2016
• Start date: April 2014
• Est. completion date: April 2017

Study information

• Verified date: June 2016
• Source: Affiliated Hospital to Academy of Military Medical Sciences
• Contact: Hongmei Ning, M.D., Ph.D.
• Phone: +86 10 66947405
• Email: ninghongmei72[@]sina.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 65 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft vs Host Disease
• Graft-versus-host Disease
• Hematopoietic Stem Cell Transplantation

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
China	Department of Hematopoietic Stem Cell Transplantation	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital to Academy of Military Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Acute GVHD Grades II-IV		1 Year	Yes
Secondary	Incidence of Acute GVHD Grades III-IV		By day +100 post-HSCT	Yes
Secondary	Incidence of Chronic GVHD		1 Year	Yes
Secondary	Hematologic Recovery (Neutrophils and Platelets)		Up to day +100 post-HSCT	No
Secondary	Disease Relapse or Progression		1 Year	No
Secondary	Incidence of Transplant-Related Mortality		By day +100 post-HSCT	Yes
Secondary	Frequency of Grade 3 or Greater Toxicities		Up to day +100 post-HSCT	Yes
Secondary	Incidence of Grade 2 and 3 Infections		1 Year	No
Secondary	Overall Survival		1 Year	No