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

NCT ID: NCT02799888

Last Updated: 2016-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-30

Study Completion Date

2017-04-30

Brief Summary

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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

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Conditions

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Graft-versus-host Disease Hematopoietic Stem Cell Transplantation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Maraviroc

Intervention Type DRUG

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)

Intervention Type DRUG

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)

Intervention Type DRUG

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

Intervention Type DRUG

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.

Interventions

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Maraviroc

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

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Selzentry Sandimmune Gengraf Neoral Prograf® FK506 MTX

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Affiliated Hospital to Academy of Military Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hu Chen, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Affiliated Hospital to Academy of Military Medical Sciences

Locations

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Department of Hematopoietic Stem Cell Transplantation

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Hongmei Ning, M.D., Ph.D.

Role: CONTACT

+86 10 66947405

Yongfeng Su, M.D., Ph.D.

Role: CONTACT

+86 10 66947122

Other Identifiers

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307-maraviroc-001

Identifier Type: -

Identifier Source: org_study_id

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