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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01951885
First received: September 24, 2013
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
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
Drug: tacrolimus
Drug: methotrexate
Drug: Mycophenolate mofetil
Drug: Methotrexate (low dose)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Tacrolimus, Mini-dose Methotrexate and Mycophenolate Mofetil Versus Tacrolimus and Methotrexate for the Prevention of Acute Graft-versus-Host-Disease

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Incidence of severe (grade 3-4) mucositis graded according to the World Health Organization (WHO) grading scale [ Time Frame: Up to day 28 ] [ Designated as safety issue: No ]
    Patients will be graded three times per week through day 28 of the study. Incidence will be compared through Wilcoxon rank sum tests.

  • Time to neutrophil engraftment [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    The number of days to reach a neutrophil count of greater than or equal to 500/ul for three consecutive laboratory values obtained on different days. The day of engraftment will be the first day of the three consecutive laboratory values.

  • Time to platelet engraftment [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    The number of days to reach a platelet count of greater than or equal to 20,000/ul for three consecutive laboratory values obtained on different days, independent of platelet transfusions the prior 7 days. The day of engraftment will be the first day of the three consecutive laboratory values.

  • Incidence of acute GVHD [ Time Frame: Day 7- Day 100 ] [ Designated as safety issue: No ]
    Acute GVHD will be estimated using cumulative incidence methods and compared using the Pepe-Mori test.


Secondary Outcome Measures:
  • Length of hospitalization [ Time Frame: Date of transplant to date of discharge, assessed up to 1 year ] [ Designated as safety issue: No ]
    Hospital stay will be compared between patients in groups A and B using the Wilcoxon rank sum test.

  • Use of total parenteral nutrition (TPN) [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]
    TPN and 100-day incidence of complications will be compared using the Chi-square test.

  • Overall survival defined by Center for International Blood and Marrow Transplant Research (CIBMTR) criteria for individual diseases [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and compared between the 2 groups using the log-rank test.

  • Progression-free survival defined by CIBMTR criteria for individual diseases [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method and compared between the 2 groups using the log-rank test.

  • Incidence of chronic GVHD [ Time Frame: after Day +100, every 3 months ] [ Designated as safety issue: No ]
    Chronic GVHD will be graded as mild, moderate, or severe based on the National Institutes of Health Consensus Development Project.The type and duration of immunosuppressive treatment given for cGVHD will be recorded.

  • Length of time on continuous infusion narcotics [ Time Frame: up to +28 day ] [ Designated as safety issue: No ]
    Start and stop dates for the need of continuous IV infusion of narcotics for severe mucositis pain will be recorded. Time on IV infusion will be compared between patients in groups A and B using the Wilcoxon rank sum test.

  • Incidence of infection [ Time Frame: Up to day +100 ] [ Designated as safety issue: No ]
    TPN and 100-day incidence of infection will be compared using a Chi-square test. Infection will be monitored up to one year after transplantation

  • Incidence of hepatotoxicity [ Time Frame: Up to day +100 ] [ Designated as safety issue: No ]
    TPN and 100-day incidence of hepatotoxicity will be compared using a Chi-square test. Hepatotoxicity will be monitored up to one year after transplantation

  • Incidence of nephrotoxicity [ Time Frame: Up to day +100 ] [ Designated as safety issue: No ]
    TPN and 100-day incidence of nephrotoxicity will be compared using a Chi-square test. Nephrotoxicity will be monitored up to one year after transplantation

  • Incidence of pulmonary toxicity [ Time Frame: Up to day +180 ] [ Designated as safety issue: No ]
    TPN and 180-day incidence of pulmonary toxicity will be compared using a Chi-square test. Pulmonary toxicity will be monitored up to one year after transplantation


Other Outcome Measures:
  • Chimerism results [ Time Frame: Up to one year ] [ Designated as safety issue: No ]
    Donor chimerism will be assessed by analysis of single-tandem repeats on whole marrow and in lymphocyte enriched or sorted CD3+ T cells and CD33+ granulocytes. Blood will be obtained for donor chimerism "Bone Marrow Engraftment analysis" at approximately 1, 2, 3, 6, 9 and 12 months or as clinically indicated.


Estimated Enrollment: 100
Study Start Date: May 2014
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
Drug: tacrolimus
Tacrolimus 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
Other Names:
  • FK 506
  • Prograf
Drug: methotrexate
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.
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Experimental: 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 mycophenolate mofetil IV BID or PO BID beginning on day 1, with a taper from day 45 to day 100 (in the absence of GVHD).
Drug: tacrolimus
Tacrolimus 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
Other Names:
  • FK 506
  • Prograf
Drug: Mycophenolate mofetil
Mycophenolate 1000mg IV twice daily will begin on day +1, and will be converted to oral administration 1000 mg twice a day once patient can tolerate oral route. Patients<40 kg will receive MMF 45 mg/kg/day (15mg/kg IV three times a day).
Other Names:
  • Cellcept
  • MMF
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.
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01951885

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Betty Hamilton, MD    216-444-2529    hamiltb2@ccf.org   
Principal Investigator: Betty Hamilton, MD         
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Withdrawn
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Betty Hamilton, MD Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01951885     History of Changes
Other Study ID Numbers: CASE6Z13, NCI-2013-01800, CASE 6Z13, P30CA043703
Study First Received: September 24, 2013
Last Updated: May 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Neoplasms
Graft vs Host Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Biphenotypic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Bone Marrow Diseases
Hematologic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias

ClinicalTrials.gov processed this record on August 28, 2014