Clinical trial NCT01951885: Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention
Official title: Tacrolimus, Mini-dose Methotrexate and Mycophenolate Mofetil Versus Tacrolimus and Methotrexate for the Prevention of Acute Graft-versus-Host-Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2013-09-27
Enrollment: 101
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

Detailed 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.

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

Primary outcomes:
measure: Percentage of Severe (Grade 3-4) Mucositis Graded According to the World Health Organization (WHO) Grading Scale
timeFrame: Up to day 28
measure: Time to Neutrophil Engraftment
timeFrame: Up to 28 days
measure: Time to Platelet Engraftment
timeFrame: The date the participant engrafts, up to 28 days
measure: Cumulative Incidence of Participants With Acute GVHD
timeFrame: Day 7- Day 100
Secondary outcomes:
measure: Length of Hospitalization
timeFrame: Date of transplant to date of discharge, assessed up to 1 year
measure: Percentage of Participants Using Total Parenteral Nutrition (TPN) Within 100 Days
timeFrame: Up to day 100
measure: Overall Survival
timeFrame: Up to 1 year
measure: Progression-free Survival
timeFrame: Up to 1 year
measure: Incidence of Chronic GVHD
timeFrame: at 6 months
measure: Incidence of Chronic GVHD
timeFrame: at 12 months
measure: Length of Time on Continuous Infusion Narcotics
timeFrame: up to +28 day
measure: Incidence of Infection
timeFrame: Up to day +100
measure: Incidence of Hepatotoxicity as Measured by Bilirubin
timeFrame: Up to day +100
measure: Incidence of Hepatotoxicity as Measured by Elevated Liver Enzymes
timeFrame: Up to day +100
measure: Incidence of Hepatotoxicity as Measured by Veno-occlusive Disease (VOD)
timeFrame: Up to day +100
measure: Incidence of Nephrotoxicity
timeFrame: Up to day +100
measure: Incidence of Pulmonary Toxicity Measured by Pulmonary Hemorrhage
timeFrame: Up to day +180
measure: Incidence of Pulmonary Toxicity Measured by Pulmonary Edema
timeFrame: Up to day +180
measure: Incidence of Pulmonary Toxicity Measured by Respiratory Failure
timeFrame: Up to day +180
Other outcomes:
measure: Chimerism Results
timeFrame: Up to one year
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
name: Betty Hamilton, MD
role: PRINCIPAL_INVESTIGATOR
References: