Phase II Maraviroc for GVHD Prevention
Condition: Hematologic Malignancy
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Maraviroc 300 mg
Intervention description: Patients enrolled on this trial will receive a standard conditioning regimen with fludarabine and busulfan followed by a peripheral blood stem cell infusion from an unrelated donor, standard GVHD prophylaxis and standard antiviral and antifungal prophylaxis. In addition, all patients will receive maraviroc from day -3 to d+ 90.
Intervention MeSH terms: Maraviroc
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      RATIONALE: Successful allogeneic stem-cell transplantation is often limited by
      graft-versus-host disease (GVHD). Migration of donor cells into tissues plays a major role in
      GVHD. Drugs that block chemokine receptors such as CCR5, can potentially decrease the
      migration of donor cells into tissues. Blocking CCR5 after allogeneic stem-cell
      transplantation may therefore reduce the rates of GVHD.

      PURPOSE: This study explores the efficacy of pharmacologic inhibition of CCR5 in prevention
      of GVHDby administering maraviroc during allogeneic stem-cell transplantation with reduced
      intensity conditioning.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients ≥18 years of age with a hematologic malignancy other than aplastic anemia or
             primary myelofibrosis, scheduled to undergo RIC allogeneic SCT with a peripheral blood
             stem cell graft from an unrelated donor, using Flu/Bu conditioning and Tac/MTX GVHD
             prophylaxis. The following diagnoses are included:

               -  Acute leukemia - AML, ALL or acute biphenotypic leukemia. Patients will have
                  documentation of complete remission within 6 weeks prior to their transplant.
                  Complete remission is defined as <5% blasts on a bone marrow biopsy and absence
                  of any known extramedullary disease.

               -  Chronic myelogenous leukemia in any stage, but with documentation of <5% blasts
                  on a bone marrow biopsy within 6 weeks prior to transplant.

               -  Myelodysplastic syndrome of any subtype, but with documentation of <5% blasts on
                  a bone marrow biopsy within 6 weeks prior to transplant.

               -  Myeloproliferative disorders other than primary myelofibrosis.

               -  Lymphoma - All types of lymphoma are eligible.

               -  CLL and PLL.

          -  Patients who meet institutional eligibility criteria for allogeneic SCT:

               -  Renal function: Serum creatinine ≤2.

               -  Hepatic function: Baseline direct bilirubin, ALT or AST lower than three times
                  the upper limit of normal.

               -  Pulmonary disease: FVC or FEV1 ≥ 40% predicted.

               -  Cardiac ejection fraction ≥ 40%.

          -  Availability of an unrelated donor, identified and screened by the NMDP. The donor
             will have at least 7/8 HLA-A, -B, -C and -DRB1 matching by high resolution molecular
             typing and will meet NMDP eligibility criteria to serve as a peripheral blood
             stem-cell donor.

          -  Karnofsky score ≥ 70% at the time of screening.

          -  Capacity to understand and sign the study informed consent form.

          -  Negative pregnancy test. Women of childbearing potential (not having had a
             hysterectomy, a bilateral oophorectomy or bilateral tubal ligation, or be
             post-menopausal with a total cessation of menses of > 1 year) must agree to use
             documented reliable method(s) of contraception. Men should agree to use condoms during
             the study period.

               -  Co-enrollment in other clinical trials that do not include experimental GVHD
                  therapies is allowed.

        Exclusion Criteria

          -  Patients with aplastic anemia or primary myelofibrosis. Patients with marrow fibrosis
             secondary to MDS, AML or a myeloproliferative disorder other than primary
             myelofibrosis are eligible.

          -  Patients who are not expected to be available for follow-up in our institution for at
             least 180 days after the transplant.

          -  Prior allogeneic SCT.

          -  Uncontrolled bacterial, viral or fungal infections.

          -  Patients who receive maraviroc for the treatment of HIV infection.

          -  Patients receiving other investigational drugs for GVHD.

          -  Co-enrollment in other clinical trials that do not include experimental GVHD therapies
             is allowed.

          -  Patients with prior malignancies are excluded unless treated with curative intent and
             known to be free of disease for at least 2 years.