Acute Graft Versus Host DiseasePhase 2NCT00803010
Graft-Versus-Host Disease (GVHD) Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation
A Phase 2 study testing Tacrolimus (TAC), Methotrexate (MTX) and Rapamycin (RAPA) in people with Acute Graft Versus Host Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Acute Graft Versus Host Disease
- What is being tested?
- Tacrolimus (TAC), Methotrexate (MTX) and Rapamycin (RAPA)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%.
Who cannot join
- Those with any Sorror's co-morbidity factors with score > 3
- 2 or more Sorror's factors with composite score of ≥ 3
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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.
- Conditions
- Acute Graft Versus Host Disease
- Being tested
- Tacrolimus (TAC), Methotrexate (MTX), Rapamycin (RAPA)
- Keywords
- Acute Graft Versus Host Disease (aGVHD), GVHD, graft-versus-host disease, tacrolimus, sirolimus, methotrexate, combination therapy, GVHD prophylaxis
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tacrolimus (TAC)Drug
Also called FK-506, fujimycin, Prograf, Advagraf
Tacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3.
Methotrexate (MTX)Drug
Also called Trexall, Rheumatrex
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.
Rapamycin (RAPA)Drug
Also called Sirolimus
Rapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily.
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus / Rapamycin (TAC/RAPA) | Active comparator | 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. Receives: Drug: Tacrolimus (TAC); Drug: Rapamycin (RAPA) |
| Tacrolimus / Methotrexate (TAC/MTX) | Active comparator | Tacrolimus: beginning 3 days before transplant and given for at least 50 days.
Methotrexate: given on days 1, 3, 6 and 11, after transplant. Receives: Drug: Tacrolimus (TAC); Drug: Methotrexate (MTX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 100 Days Post Transplant
Secondary outcomes (2)
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).
Measured: 30 days and 90 days
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 .
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2008 (estimated)
- Study startSep 2008
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claudio Anasetti, MD, Study director, HLeeMoffittCancerCenter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00803010
- Sponsor's protocol ID
- MCC-15372
- Other IDs
- IRB 106591
- Status last verified
- Dec 2013
- First submitted
- 4 Dec 2008
- Last updated
- 31 Jul 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 22689677
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Tacrolimus and Rapamycin vs. Tacrolimus and Methotrexate as GVHD Prophylaxis After Allogeneic Peripheral Blood Hematopoietic Cell Transplantation
- ClinicalTrials.gov ID
- NCT00803010
- Acronym / sponsor ID
- MCC-15372
- Conditions
- Acute Graft Versus Host Disease
- Keywords
- Acute Graft Versus Host Disease (aGVHD), GVHD, graft-versus-host disease, tacrolimus, sirolimus, methotrexate, combination therapy, GVHD prophylaxis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Study start
- Sep 2008
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 5 Dec 2008 (estimated)
- Results
- Posted 5 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus / Rapamycin (TAC/RAPA) | Active comparator | Drug: Tacrolimus (TAC), Drug: Rapamycin (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. |
| Tacrolimus / Methotrexate (TAC/MTX) | Active comparator | Drug: Tacrolimus (TAC), Drug: Methotrexate (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. |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- Those with any Sorror's co-morbidity factors with score > 3
- 2 or more Sorror's factors with composite score of ≥ 3
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tacrolimus (TAC)Also: FK-506, fujimycin, Prograf, AdvagrafTacrolimus: administered at 0.02 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3. | Drug | Tacrolimus / Methotrexate (TAC/MTX), Tacrolimus / Rapamycin (TAC/RAPA) |
| Methotrexate (MTX)Also: Trexall, RheumatrexMethotrexate: 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. | Drug | Tacrolimus / Methotrexate (TAC/MTX) |
| Rapamycin (RAPA)Also: SirolimusRapamycin: initially as 9 mg oral loading dose on day -1. Thereafter, administered as an oral regimen of 4 mg daily. | Drug | Tacrolimus / Rapamycin (TAC/RAPA) |
Primary outcome
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
2 secondary outcomes
Incidence of Increased Absolute Numbers of Regulatory T Cells (Treg)
Time frame: 30 days and 90 days
2 Year Post Transplant Overall Survival (OS) Rate
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22689677Pidala 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.
- H.Lee Moffitt Cancer Center \& Research InstituteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claudio Anasetti, MD study director
HLeeMoffittCancerCenter
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tacrolimus (TAC), Methotrexate (MTX) and Rapamycin (RAPA) in people with Acute Graft Versus Host Disease, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Evidence of Acute Graft Versus Host Disease (aGVHD), Post Transplant (time frame: 100 Days Post Transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00803010, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2015.