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

July 10, 2015 updated by: H. Lee Moffitt Cancer Center and Research Institute

Phase II Trial of Tacrolimus and Rapamycin vs. Tacrolimus and Methotrexate as GVHD Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H.Lee Moffitt Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Prograf
  • Protopic
  • FK-506
  • Advagraf
  • fujimycin
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 Names:
  • 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:
  • Prograf
  • Protopic
  • FK-506
  • Advagraf
  • fujimycin
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:
  • Rheumatrex
  • Trexall

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant
Time Frame: 100 Days Post Transplant

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
100 Days Post Transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg)
Time Frame: 30 days and 90 days
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 employed to test differences in percent Treg (% Treg/total CD4+ cells).
30 days and 90 days
2 Year Post Transplant Overall Survival (OS) Rate
Time Frame: 2 years
Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Investigators

  • Study Director: Claudio Anasetti, MD, HLeeMoffittCancerCenter

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

December 4, 2008

First Submitted That Met QC Criteria

December 4, 2008

First Posted (Estimate)

December 5, 2008

Study Record Updates

Last Update Posted (Estimate)

July 31, 2015

Last Update Submitted That Met QC Criteria

July 10, 2015

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCC-15372
  • IRB 106591

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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