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

Affiliated Hospital to Academy of Military Medical Sciences

Status and phase: Unknown; Phase 2

Conditions: Graft-versus-host Disease; Hematopoietic Stem Cell Transplantation

Treatments: Drug: Tacrolimus (in HLA-Mismatched Related Donor Transplantation); Drug: Maraviroc; Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation); Drug: Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT02799888

307-maraviroc-001

Details and patient eligibility

About

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.

Enrollment: 40 estimated patients

Sex: All

Ages: 12 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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40 participants in 1 patient group

Maraviroc + standard GVHD prophylaxis

Experimental group

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.

Treatment:

Drug: Cyclosporine (in HLA-Unrelated Donor Transplantation)

Drug: Maraviroc

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

Drug: Methotrexate