Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention
Condition: Chronic Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Acute Biphenotypic Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Hodgkins Disease; Chronic Lymphocytic Leukemia; Multiple Myeloma
MeSH terms: Leukemia; Multiple Myeloma; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders
Intervention: tacrolimus; methotrexate; Mycophenolate mofetil; Methotrexate (low dose)
Intervention description: Tacrolimus 0.03 mg/kg/day beginning day -1 or tacrolimus 0.03mg/kg/dose BID orally beginning on day -3. If Tac is administered intravenously, it will be given over 24 hours and will be converted to oral administration 2 times a day when the patient has engrafted and/or can tolerate oral medication. Levels of Tac will be obtained to maintain a recommended target serum level of 5-12 ng/mL; MTX 15mg/m2 IV on day +1, followed by 10mg/m2 on day +3, +6, +11. If patient < 10 kg then MTX will be given at 0.5 mg/kg IV on day +1. Then MTX will be given at 0.33 mg/kg on days +3, +6 and +11.; Patients will receive Mycophenolate beginning on day +1. Patients >40 kg will receive Mycophenolate 1000 mg twice a day. Mycophenolate should be given orally twice a day. IV formulation may be used if the patient cannot tolerate oral route. Patients < 40 kg will receive MMF 45 mg/kg/day (15 mg/kg three times a day). MMF may be given orally or intravenously as per institutional protocol; MTX 5mg/m2 IV on day +1, +3, +6. If patient<10 kg MTX will be given at 0.17 mg/kg on day +1, +3, and +6.
Intervention MeSH terms: Mycophenolic Acid; Methotrexate; Tacrolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This randomized clinical trial studies standard GVHD prophylaxis with tacrolimus and
      methotrexate compared to tacrolimus, mycophenolate mofetil and a reduced-dose methotrexate in
      patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplant.
      Both mycophenolate mofetil and reduced-dose methotrexate, in combination with a calcineurin
      inhibitor, have been shown to be safe and effective in GVHD prevention with less toxicity
      than standard dose methotrexate. It is not yet known, however, whether this combination of
      mycophenolate mofetil and reduced-dose methotrexate with tacrolimus is more effective than
      tacrolimus and standard dose methotrexate in preventing GVHD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have one of the following documented diseases:

               -  Chronic myelogenous leukemia

               -  Chronic lymphocytic leukemia

               -  Multiple myeloma

               -  Myelodysplasia

               -  Myeloproliferative disorder

               -  Non-Hodgkin's lymphoma

               -  Hodgkin's disease

               -  Acute myelogenous leukemia

               -  Acute lymphoblastic leukemia

               -  Acute biphenotypic leukemia

          -  Patients must be undergoing a myeloablative allogeneic hematopoietic cell transplant
             with one of the following conditioning regimens:

               -  Busulfan (≥ 12.8 mg/kg IV or PO) and cyclophosphamide (≥ 120 mg/kg)

                  --- Busulfan dose may be adjusted according to pharmacokinetics targeting a daily
                  AUC of 5000 μmol-min/L, per institution standard of practice.

               -  Total body irradiation (TBI) (≥ 1200 cGy) and etoposide (60 mg/kg)

               -  TBI (≥ 1200 cGy) and cyclophosphamide (120 mg/kg)

          -  Patient must have achieved and be in complete morphologic remission prior to starting
             conditioning regimen

          -  Patient's donor must be a related or unrelated human leukocyte antigen (HLA) 8/8
             allele-level match (HLA-A, B, C and DRB1)

          -  Adult patients must have an Eastern Cooperative Oncology Group (ECOG) performance
             status of 0 or 1; pediatric patients must have Lansky score ≥ 60%

          -  Patients must have a life expectancy of 100 days

          -  Patients must sign written informed consent

        Exclusion Criteria:

          -  Patients who have undergone any prior transplant

          -  Patients who are seropositive for human immunodeficiency virus (HIV)

          -  Patients with any medical illness or concurrent psychiatric illness which, in the
             investigators' opinion, cannot be adequately controlled with appropriate therapy

          -  Patients who are pregnant or lactating