Tacrolimus/Sirolimus/Methotrexate vs Tacrolimus/Methotrexate or Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis After Reduced Intensity Allogeneic Stem Cell Transplantation for Patients With Lymphoma
Status: | Completed |
---|---|
Conditions: | Lymphoma |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - 72 |
Updated: | 2/3/2019 |
Start Date: | June 2009 |
End Date: | November 2014 |
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.
(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.
- 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.
"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.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- 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)
We found this trial at
5
sites
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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Emory University Hospital As the largest health care system in Georgia and the only health...
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Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
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