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

Primary Purpose

Acute Graft Versus Host Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tacrolimus (TAC)

Methotrexate (MTX)

Rapamycin (RAPA)

About this trial

This is an interventional prevention trial for Acute Graft Versus Host Disease focused on measuring Acute Graft Versus Host Disease (aGVHD), GVHD, graft-versus-host disease, tacrolimus, sirolimus, methotrexate, combination therapy, GVHD prophylaxis

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

H.Lee Moffitt Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Tacrolimus / Rapamycin (TAC/RAPA)

Tacrolimus / Methotrexate (TAC/MTX)

Arm Description

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.

Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant.

Outcomes

Primary Outcome Measures

Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), 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: classic acute GVHD - onset within 100 days after transplant persistent - acute GVHD with onset prior to day 100 and without resolution beyond day 100 recurrent - acute GVHD recurrent after prior episode of acute GVHD 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)

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).

2 Year Post Transplant Overall Survival (OS) Rate

Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .

Full Information

NCT ID

NCT00803010

First Posted

December 4, 2008

Last Updated

July 10, 2015

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT00803010

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2013

Overall Recruitment Status

Completed

Study Start Date

September 2008 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Graft Versus Host Disease

Keywords

Acute Graft Versus Host Disease (aGVHD), GVHD, graft-versus-host disease, tacrolimus, sirolimus, methotrexate, combination therapy, GVHD prophylaxis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

74 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tacrolimus / Rapamycin (TAC/RAPA)

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Tacrolimus / Methotrexate (TAC/MTX)

Arm Type

Active Comparator

Arm Description

Tacrolimus: beginning 3 days before transplant and given for at least 50 days. Methotrexate: given on days 1, 3, 6 and 11, after transplant.

Intervention Type

Drug

Intervention Name(s)

Tacrolimus (TAC)

Other Intervention Name(s)

FK-506, fujimycin, Prograf, Advagraf, Protopic

Intervention Description

Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.

Intervention Type

Drug

Intervention Name(s)

Methotrexate (MTX)

Other Intervention Name(s)

Trexall, Rheumatrex

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Rapamycin (RAPA)

Other Intervention Name(s)

Sirolimus

Intervention Description

Rapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.

Primary Outcome Measure Information:

Title

Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant

Description

Time Frame

100 Days Post Transplant

Secondary Outcome Measure Information:

Title

Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg)

Description

Time Frame

30 days and 90 days

Title

2 Year Post Transplant Overall Survival (OS) Rate

Description

Defined as time from transplantation (day 0 as day of stem cell infusion per standard nomenclature) to death from any cause .

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Claudio Anasetti, MD

Organizational Affiliation

HLeeMoffittCancerCenter

Official's Role

Study Director

Facility Information:

Facility Name

H.Lee Moffitt Cancer Center

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22689677

Citation

Pidala J, Kim J, Jim H, Kharfan-Dabaja MA, Nishihori T, Fernandez HF, Tomblyn M, Perez L, Perkins J, Xu M, Janssen WE, Veerapathran A, Betts BC, Locke FL, Ayala E, Field T, Ochoa L, Alsina M, Anasetti C. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012 Dec;97(12):1882-9. doi: 10.3324/haematol.2012.067140. Epub 2012 Jun 11.

Results Reference

derived

Links:

URL

http://www.moffitt.org/

Description

H.Lee Moffitt Cancer Center & Research Institute

Learn more about this trial

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

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