Non-hodgkin LymphomaPhase 3NCT00928018
Tacrolimus/Sirolimus/Methotrexate vs Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
A Phase 3 study testing Sirolimus, Methotrexate and Tacrolimus in people with Non-hodgkin Lymphoma and Hodgkin Lymphoma, run by Dana-Farber Cancer Institute at 5 sites in United States.
Trial summary
This trial is comparing whether using a drug called sirolimus for graft versus host disease (GVHD) prevention can decrease the chance of the participant's lymphoma relapsing after transplantation, compared to using a standard GVHD prevention regimen without sirolimus. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Non-hodgkin Lymphoma, Hodgkin Lymphoma
- What is being tested?
- Sirolimus, Methotrexate and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2009to Nov 2014
- Phase
- Phase 3
- 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 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible if their primary indication for transplantation is among the following: Indolent B-cell non-Hodgkin lymphoma (NHL); Aggressive B-Cell NHL; T-cell NHL; or Hodgkin Lymphoma.
- Patients must have one of the following combinations of disease status and disease histology at the time of enrollment: 1) Patients may be transplanted as part of first-line therapy if they have one of the following histologies: CLL with adverse cytogenetics, MCL or, T-cell NHL. 2) Patients may be transplanted as part of treatment for relapsed or refractory disease without a prior autologous transplantation of they have one of the following histologies: Indolent NHL (including CLL/SLL), MCL or T-cell NHL. 3) Patients may be transplanted as part of treatment for disease that has relapsed or progressed after autologous transplantation if they have any of the histologies listed above. Patients may also be enrolled without a prior autologous transplantation if they have a contraindication to autologous transplantation, in the opinion of the treating clinician. 4) There is no minimal or maximal time interval from the patient's last anti-lymphoma therapy and the time of transplantation.
- 18-72 years of age
- Matched related or matched unrelated donor
- Donor willing to donate peripheral blood stem cells and meeting institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells according to individual transplant center criteria.
Who cannot join
- Patients with Burkitt lymphoma or DLBCL with a c-myc rearrangement
- Karnofsky performance status of less than 70% at the time of registration
- Prior allogeneic stem cell transplantation (note that prior autologous stem cell transplantation is allowed)
- Uncontrolled infection
- Serum creatinine 2.0mg/dl or greater
- Total bilirubin 2.0mg/dl or greater (unless related to hemolysis or Gilbert's syndrome)
Show all 13Show fewer
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times or greater than the institutional upper limit of normal
- Left ventricular ejection fraction < 30%
- Cholesterol > 500mg/dl or triglycerides > 500 mg/dl despite appropriate treatment
- Seropositivity for HIV
- Pregnancy or breast-feeding (effective contraception must be used during therapy and for at least 6 months after the end of immunosuppressive agents)
- Prior history of allergy to sirolimus, tacrolimus, cyclosporine, methotrexate or MMF
- Concomitant treatment with another investigational drug (unless cleared by study chair)
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory University Hospital
Atlanta, Georgia, 30322
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Ohio State University
Columbus, Ohio, 43210
University of Minnesota
Minneapolis, Minnesota, 55454
About this study
Official title: A Phase III Multicenter, Randomized Trial Comparing Tacrolimus/Sirolimus/Methotrexate Versus Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
This trial is comparing whether using a drug called sirolimus for graft versus host disease (GVHD) prevention can decrease the chance of the participant's lymphoma relapsing after transplantation, compared to using a standard GVHD prevention regimen without sirolimus. Since mTOR inhibitors have anti-lymphoma activity, their use after transplantation may lead to a decreased risk of relapse and hence better transplantation outcome.
Read the detailed description
- Because no one knows which of the study options is best, participants will be "randomized" into one of the two possible groups for GVHD prophylaxis: 1) a sirolimus-containing regimen (tacrolimus, sirolimus and methotrexate) or 2) a sirolimus-free regimen (tacrolimus and methotrexate or cyclosporine and mycophenolate mofetil).
- Participants will receive a reduced intensity conditioning regimen. This is done to prepare the body for transplantation. This will consist of a combination of drugs (either fludarabine and busulfan or fludarabine, cyclophosphamide and low-dose total body irradiation). The purpose of these drugs is to weaken the immune system and lower the chance of the body rejecting the donated stem cells.
- Participants will also receive the GVHD prophylaxis regimen that they have been randomized to. These drugs will lower the chance of rejecting the donor cells and lower the chance of developing GVHD.
- Conditions
- Non-hodgkin Lymphoma, Hodgkin Lymphoma
- Being tested
- Sirolimus, Methotrexate, Tacrolimus, Cyclosporine, MMF
- Keywords
- allogeneic stem cell transplant, reduced intensity conditioning, graft versus host disease, GVHD, RIC transplantation
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hodgkin Disease, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
Taken orally for at least 12 months
MethotrexateDrug
Also called Abbreviated MTX, Trade name:Trexall
Given intravenously on the first, third and sixth day after transplant
TacrolimusDrug
Also called Prograf
Taken orally or given intravenously for at least 6 months
CyclosporineDrug
Also called Brand names:, •Gengraf, •Neoral, •Sandimmune
Taken orally or given intravenously for at least 6 months
MMFDrug
Also called Mycophenolate mofetil (MMF), Brand Names:, CellCept, Myfortic
Taken orally for about 2 months
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus-Containing Regimen | Active comparator | The Sirolimus containing arm will consist of the following drugs:
Experimental Arm: tacrolimus + sirolimus + low-dose methotrexate
Tacrolimus: Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3.
Sirolimus:Given as a loading oral dose of 12 mg on day -3, then as a daily maintenance dose of 4 mg starting on day -2.
Methotrexate: Administered by intravenous bolus infusion, per institutional standard, at a dose of 5 mg/m2 on days +1, +3 and +6. Receives: Drug: Sirolimus; Drug: Methotrexate; Drug: Tacrolimus |
| Sirolimus-Free regimen | Active comparator | There are two choices for the Sirolimus free arm:
Control Arm 1: tacrolimus + methotrexate
Tacrolimus:Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3.
Methotrexate:Administered by intravenous bolus infusion at a dose of 5 mg/m2 on days +1, +3 and +6. For patients receiving stem cells from unrelated donors, an additional dose will be given on day +11.
Control Arm 2: cyclosporine + MMF
Cyclosporine: administered orally at a dose of 6 mg/kg based on ABW bid starting on day -3.
MMF:administered at a dose of 3gm daily orally (or intravenously if the patient cannot tolerate oral administration) divided in 2 or 3 doses (bid or tid) depending on physician preference starting on day 3. Receives: Drug: Methotrexate; Drug: Tacrolimus; Drug: Cyclosporine; Drug: MMF |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Compare 2-year Overall Survival of Patients With Lymphoma Undergoing RIC SCT Between Those Receiving Tacrolimus/Sirolimus/Methotrexate and Those Receiving Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil
Measured: 2 years
Secondary outcomes (5)
To Compare 2-year Progression-free Survival Between the Two Treatment Arms
Measured: 2 years
To Compare the 2-year Cumulative Incidences of Disease Progression and of Non-relapse Mortality Between the Two Treatment Arms
Measured: 2 years
To Compare the 180-day Cumulative Incidence of Grades II-IV and Grades III-IV Acute GVHD Between the Two Treatment Arms
Measured: 6 months
To Compare the 2-year Cumulative Incidence of Chronic GVHD Between the Two Treatment Arms.
Measured: 2 years
To Compare the 2-year of Overall Survival, Progression-free Survival, Cumulative Incidences of Progression and Non-relapse Mortality Between the Treatment Arms for Each Histology Studied.
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 posted25 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionNov 2014
- Study completionNov 2014
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 Non-hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Philippe Armand, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Philippe Armand, MD, PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928018
- Sponsor's protocol ID
- 09-073
- Other IDs
- CA142106
- Status last verified
- Jan 2019
- First submitted
- 24 Jun 2009
- Last updated
- 1 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Armand P, Kim HT, Sainvil MM, Lange PB, Giardino AA, Bachanova V, Devine SM, Waller EK, Jagirdar N, Herrera AF, Cutler C, Ho VT, Koreth J, Alyea EP, McAfee SL, Soiffer RJ, Chen YB, Antin JH. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial. Br J Haematol. 2016 Apr;173(1):96-104. doi: 10.1111/bjh.13931. Epub 2016 Jan 5.
PubMed 26729448
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Multicenter, Randomized Trial Comparing Tacrolimus/Sirolimus/Methotrexate Versus Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
- ClinicalTrials.gov ID
- NCT00928018
- Acronym / sponsor ID
- 09-073
- Conditions
- Non-hodgkin Lymphoma, Hodgkin Lymphoma
- Keywords
- allogeneic stem cell transplant, reduced intensity conditioning, graft versus host disease, GVHD, RIC transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Massachusetts General Hospital, National Cancer Institute (NCI)
- Study start
- Jun 2009
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Posted 18 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is comparing whether using a drug called sirolimus for graft versus host disease (GVHD) prevention can decrease the chance of the participant's lymphoma relapsing after transplantation, compared to using a standard GVHD prevention regimen without sirolimus. Since mTOR inhibitors have anti-lymphoma activity, their use after transplantation may lead to a decreased risk of relapse and hence better transplantation outcome.
Detailed description
- Because no one knows which of the study options is best, participants will be "randomized" into one of the two possible groups for GVHD prophylaxis: 1) a sirolimus-containing regimen (tacrolimus, sirolimus and methotrexate) or 2) a sirolimus-free regimen (tacrolimus and methotrexate or cyclosporine and mycophenolate mofetil).
- Participants will receive a reduced intensity conditioning regimen. This is done to prepare the body for transplantation. This will consist of a combination of drugs (either fludarabine and busulfan or fludarabine, cyclophosphamide and low-dose total body irradiation). The purpose of these drugs is to weaken the immune system and lower the chance of the body rejecting the donated stem cells.
- Participants will also receive the GVHD prophylaxis regimen that they have been randomized to. These drugs will lower the chance of rejecting the donor cells and lower the chance of developing GVHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus-Containing Regimen | Active comparator | Drug: Sirolimus, Drug: Methotrexate, Drug: TacrolimusThe Sirolimus containing arm will consist of the following drugs: Experimental Arm: tacrolimus + sirolimus + low-dose methotrexate Tacrolimus: Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3. Sirolimus:Given as a loading oral dose of 12 mg on day -3, then as a daily maintenance dose of 4 mg starting on day -2. Methotrexate: Administered by intravenous bolus infusion, per institutional standard, at a dose of 5 mg/m2 on days +1, +3 and +6. |
| Sirolimus-Free regimen | Active comparator | Drug: Methotrexate, Drug: Tacrolimus, Drug: Cyclosporine, Drug: MMFThere are two choices for the Sirolimus free arm: Control Arm 1: tacrolimus + methotrexate Tacrolimus:Administered orally at a dose of 0.05 mg/kg based on ABW bid starting on day -3. Methotrexate:Administered by intravenous bolus infusion at a dose of 5 mg/m2 on days +1, +3 and +6. For patients receiving stem cells from unrelated donors, an additional dose will be given on day +11. Control Arm 2: cyclosporine + MMF Cyclosporine: administered orally at a dose of 6 mg/kg based on ABW bid starting on day -3. MMF:administered at a dose of 3gm daily orally (or intravenously if the patient cannot tolerate oral administration) divided in 2 or 3 doses (bid or tid) depending on physician preference starting on day 3. |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients will be eligible if their primary indication for transplantation is among the following: Indolent B-cell non-Hodgkin lymphoma (NHL); Aggressive B-Cell NHL; T-cell NHL; or Hodgkin Lymphoma.
- Patients must have one of the following combinations of disease status and disease histology at the time of enrollment: 1) Patients may be transplanted as part of first-line therapy if they have one of the following histologies: CLL with adverse cytogenetics, MCL or, T-cell NHL. 2) Patients may be transplanted as part of treatment for relapsed or refractory disease without a prior autologous transplantation of they have one of the following histologies: Indolent NHL (including CLL/SLL), MCL or T-cell NHL. 3) Patients may be transplanted as part of treatment for disease that has relapsed or progressed after autologous transplantation if they have any of the histologies listed above. Patients may also be enrolled without a prior autologous transplantation if they have a contraindication to autologous transplantation, in the opinion of the treating clinician. 4) There is no minimal or maximal time interval from the patient's last anti-lymphoma therapy and the time of transplantation.
- 18-72 years of age
- Matched related or matched unrelated donor
- Donor willing to donate peripheral blood stem cells and meeting institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells according to individual transplant center criteria.
Key exclusion criteria (13 listed)
- Patients with Burkitt lymphoma or DLBCL with a c-myc rearrangement
- Karnofsky performance status of less than 70% at the time of registration
- Prior allogeneic stem cell transplantation (note that prior autologous stem cell transplantation is allowed)
- Uncontrolled infection
- Serum creatinine 2.0mg/dl or greater
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 |
|---|---|---|
| SirolimusAlso: RapamycinTaken orally for at least 12 months | Drug | Sirolimus-Containing Regimen |
| MethotrexateAlso: Abbreviated MTX, Trade name:TrexallGiven intravenously on the first, third and sixth day after transplant | Drug | Sirolimus-Containing Regimen, Sirolimus-Free regimen |
| TacrolimusAlso: PrografTaken orally or given intravenously for at least 6 months | Drug | Sirolimus-Containing Regimen, Sirolimus-Free regimen |
| CyclosporineAlso: Brand names:, •Gengraf, •Neoral, •SandimmuneTaken orally or given intravenously for at least 6 months | Drug | Sirolimus-Free regimen |
| MMFAlso: Mycophenolate mofetil (MMF), Brand Names:, CellCept, MyforticTaken orally for about 2 months | Drug | Sirolimus-Free regimen |
Primary outcome
To Compare 2-year Overall Survival of Patients With Lymphoma Undergoing RIC SCT Between Those Receiving Tacrolimus/Sirolimus/Methotrexate and Those Receiving Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil
Time frame: 2 years
5 secondary outcomes
To Compare 2-year Progression-free Survival Between the Two Treatment Arms
Time frame: 2 years
To Compare the 2-year Cumulative Incidences of Disease Progression and of Non-relapse Mortality Between the Two Treatment Arms
Time frame: 2 years
To Compare the 180-day Cumulative Incidence of Grades II-IV and Grades III-IV Acute GVHD Between the Two Treatment Arms
Time frame: 6 months
To Compare the 2-year Cumulative Incidence of Chronic GVHD Between the Two Treatment Arms.
Time frame: 2 years
To Compare the 2-year of Overall Survival, Progression-free Survival, Cumulative Incidences of Progression and Non-relapse Mortality Between the Treatment Arms for Each Histology Studied.
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 1 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26729448Armand P, Kim HT, Sainvil MM, Lange PB, Giardino AA, Bachanova V, Devine SM, Waller EK, Jagirdar N, Herrera AF, Cutler C, Ho VT, Koreth J, Alyea EP, McAfee SL, Soiffer RJ, Chen YB, Antin JH. The addition of sirolimus to the graft-versus-host disease prophylaxis regimen in reduced intensity allogeneic stem cell transplantation for lymphoma: a multicentre randomized trial. Br J Haematol. 2016 Apr;173(1):96-104. doi: 10.1111/bjh.13931. Epub 2016 Jan 5.
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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.
Philippe Armand, MD, PhD principal investigator
Dana-Farber Cancer Institute
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus, Methotrexate and Tacrolimus in people with Non-hodgkin Lymphoma and Hodgkin Lymphoma, run by Dana-Farber Cancer Institute at 5 sites 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 5 inclusion and 13 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 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 18 Dec 2015). 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?
To Compare 2-year Overall Survival of Patients With Lymphoma Undergoing RIC SCT Between Those Receiving Tacrolimus/Sirolimus/Methotrexate and Those Receiving Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil (time frame: 2 years). 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 NCT00928018, 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 1 Feb 2019.