Chronic Myelogenous Leukemia | Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention

Chronic Myelogenous Leukemia research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

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

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:tacrolimusTacrolimus 0.03 mg/kg/day beginning day -1. Tac will be administered IV over 24 hours and will be converted to oral administration 2 times a day when the patient has engrafted and can tolerate oral medication. Levels of Tac will be obtained to maintain a recommended target serum level of 5-12 ng/mL

Drug:methotrexateMTX 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.

Drug:Mycophenolate mofetilPatients 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

Drug:Methotrexate (low dose)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.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Group A (tacrolimus, methotrexate)Patients receive tacrolimus IV over 24 hours beginning on day -1 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.

Group B (tacrolimus, methotrexate, mycophenolate mofetil)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).

Study Status


Start Date: May 21, 2014

Completed Date: July 2019

Phase: Phase 3

Type: Interventional


Primary Outcome: Incidence of severe (grade 3-4) mucositis graded according to the World Health Organization (WHO) grading scale

Secondary Outcome: Length of hospitalization

Study sponsors, principal investigator, and references

Principal Investigator: Betty Hamilton, MD

Lead Sponsor: Case Comprehensive Cancer Center

Collaborator: National Cancer Institute (NCI)

More information:

Discuss Methotrexate