Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention

Case Comprehensive Cancer Center (Case CCC)

Status and phase: Completed; Phase 3

Conditions: Acute Biphenotypic Leukemia; Multiple Myeloma; Myeloproliferative Neoplasm; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Hodgkins Disease; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin Lymphoma; Acute Myeloid Leukemia

Treatments: Drug: tacrolimus; Drug: Mycophenolate mofetil; Drug: methotrexate; Drug: Methotrexate (low dose)

Study type: Interventional

Funder types: Other

Identifiers

NCT01951885

CASE6Z13

Details and patient eligibility

About

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.

Full description

Study Design This is a prospective randomized trial to determine the effectiveness of different doses of GVHD prophylaxis on mucositis, engraftment and aGVHD. Study consists of two study groups of 50 subjects each.

Group A will receive Tac and MTX (15 mg/m2 day +1, 10 mg/m2 day +3, +6, +11). Group B will receive Tac, Mini-dose MTX (5 mg/m2 on day +1, +3, +6) and MMF.

Enrollment: 101 patients

Sex: All

Ages: Under 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

101 participants in 2 patient groups

Group A (tacrolimus, methotrexate)

Active Comparator group

Description:

Participants receive tacrolimus IV over 24 hours beginning on day -1 (or tacrolimus orally beginning on day -3) and then PO BID after engraftment with a taper from day 100 to day 180 (in the absence of GVHD). Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Treatment:

Drug: methotrexate

Drug: tacrolimus

Group B (tacrolimus, methotrexate, mycophenolate mofetil)

Experimental group

Description:

Patients receive tacrolimus as in group A and methotrexate (low dose) IV on days 1, 3, and 6. Patients also receive oral mycophenolate mofetil BID beginning on day 1, with a taper from day 45 to day 100 (in the absence of GVHD).

Treatment:

Drug: Methotrexate (low dose)

Drug: Mycophenolate mofetil

Drug: tacrolimus