Graft-Versus-Host Disease (GVHD) Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00803010
First received: December 4, 2008
Last updated: April 3, 2014
Last verified: December 2013
  Purpose

The purpose of this research is to compare the effectiveness of Tacrolimus and Rapamycin to Tacrolimus and Methotrexate in the prevention of severe graft-versus-host-disease. Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). An allogeneic hematopoietic cell transplant is a transplant using bone marrow and blood cells that come from someone other than the patient (a donor).


Condition Intervention Phase
Acute Graft Versus Host Disease
Drug: Tacrolimus (TAC)
Drug: Methotrexate (MTX)
Drug: Rapamycin (RAPA)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Trial of Tacrolimus and Rapamycin vs. Tacrolimus and Methotrexate as GVHD Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant [ Time Frame: 100 Days Post Transplant ] [ Designated as safety issue: No ]

    Incidence of acute graft versus host disease grades 2-3 according to the Common Toxicity Criteria (CTC) version 3.

    Graft-versus-host-disease (GVHD) is a risk associated with allogeneic hematopoietic cell transplants (HCT). Clinical evidence of acute GVHD was recorded per standard grading scheme.

    Acute GVHD classified as the following:

    1. classic acute GVHD - onset within 100 days after transplant
    2. persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100
    3. recurrent - acute GVHD recurrent after prior episode of acute GVHD
    4. late acute GVHD - syndrome consistent with acute GVHD, without features of chronic GVHD, with onset occurring beyond 100 days


Secondary Outcome Measures:
  • Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg) [ Time Frame: 30 days and 90 days ] [ Designated as safety issue: No ]
    Absolute numbers of Treg at designated time points according to study arm. MTX = methotrexate/tacrolimus-treated patients; SIR = sirolimus/tacrolimus-treated patients; Treg absolute number units = number of cells/microL. A two-sided Wilcoxon's rank-sum test was employe to test differences in percent Treg (% Treg/total CD4+ cells).

  • 2 Year Post Transplant Overall Survival (OS) Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .


Enrollment: 74
Study Start Date: September 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tacrolimus / Rapamycin (TAC/RAPA)

Tacrolimus: beginning 3 days before transplant and given for at least 50 days.

Rapamycin: given the day before transplant and continued daily for at least one year.

Drug: Tacrolimus (TAC)
Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.
Other Names:
  • FK-506
  • fujimycin
  • Prograf
  • Advagraf
  • Protopic
Drug: Rapamycin (RAPA)
Rapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.
Other Name: Sirolimus
Active Comparator: Tacrolimus / Methotrexate (TAC/MTX)

Tacrolimus: beginning 3 days before transplant and given for at least 50 days.

Methotrexate: given on days 1, 3, 6 and 11, after transplant.

Drug: Tacrolimus (TAC)
Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.
Other Names:
  • FK-506
  • fujimycin
  • Prograf
  • Advagraf
  • Protopic
Drug: Methotrexate (MTX)
Methotrexate: administered on day 1 at dose of 15 mg/m^2, and a dose of 10 mg/m^2 on days 3, 6, and 11. Dose can be adjusted for reduced creatinine clearance.
Other Names:
  • Trexall
  • Rheumatrex

Detailed Description:

All drugs used in this study have been used in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Methotrexate used in combination are currently used as standard of care in the prevention of graft-versus-host-disease after allogeneic hematopoietic cell transplant. Tacrolimus and Rapamycin is a newer combination we are testing to see if it would be better than Tacrolimus and Methotrexate.

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 16 and ≤ 70
  • Signed informed consent
  • Adequate vital organ function
  • No active infection, or asymptomatic infection well controlled by antibiotic HIV negative by ELISA or RT-PCR [if ELISA is positive and RT-PCR is negative, the ELISA is considered false positive]
  • Hepatitis B and C negative by serology or RT-PCR
  • Performance status: Karnofsky Performance Status Score ≥ 60%.

Exclusion Criteria:

  • Those with any Sorror's co-morbidity factors with score > 3
  • 2 or more Sorror's factors with composite score of ≥ 3
  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: NCT00803010

Locations
United States, Florida
H.Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Study Director: Claudio Anasetti, MD HLeeMoffittCancerCenter
  More Information

Additional Information:
No publications provided by H. Lee Moffitt Cancer Center and Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00803010     History of Changes
Other Study ID Numbers: MCC-15372, IRB 106591
Study First Received: December 4, 2008
Results First Received: December 10, 2013
Last Updated: April 3, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Acute Graft Versus Host Disease (aGVHD)
GVHD
graft-versus-host disease
tacrolimus
sirolimus
methotrexate
combination therapy
GVHD prophylaxis

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Methotrexate
Sirolimus
Everolimus
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on August 01, 2014