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 study is ongoing, but not recruiting participants.
Sponsor:
Dana-Farber Cancer Institute
Collaborators:
Brigham and Women's Hospital
Massachusetts General Hospital
Information provided by (Responsible Party):
Philippe Armand, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00928018
First received: June 24, 2009
Last updated: January 31, 2013
Last verified: January 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Non-hodgkin Lymphoma Hodgkin Lymphoma |
Drug: Sirolimus Drug: Methotrexate Drug: Tacrolimus Drug: Cyclosporine Drug: MMF |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Drug Information available for:
Methotrexate
Methotrexate sodium
Mycophenolic acid
Mycophenolate sodium
Sirolimus
Cyclosporine
Tacrolimus
Mycophenolate mofetil hydrochloride
Mycophenolate mofetil
Everolimus
Temsirolimus
U.S. FDA Resources
Further study details as provided by Dana-Farber Cancer Institute:
Primary Outcome Measures:
- To compare the 2-year rate of 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 ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To compare the 2-year rate of progression-free survival between the two treatment arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To compare the 2-year cumulative incidences of disease progression and of non-relapse mortality between the two treatment arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To compare the 180-day cumulative incidence of grades 2-4 and grades 3-4 acute GVHD between the two treatment arms [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- To compare the 2-year cumulative incidence of chronic GVHD between the two treatment arms. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 140 |
| Study Start Date: | June 2009 |
| Estimated Study Completion Date: | November 2014 |
| Estimated Primary Completion Date: | November 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Sirolimus-Containing Regimen
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. |
Drug: Sirolimus
Taken orally for at least 12 months
Other Name: Rapamycin
Drug: Methotrexate
Given intravenously on the first, third and sixth day after transplant
Other Names:
Drug: Tacrolimus
Taken orally or given intravenously for at least 6 months
Other Name: Prograf
|
|
Active Comparator: Sirolimus-Free regimen
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. |
Drug: Methotrexate
Given intravenously on the first, third and sixth day after transplant
Other Names:
Drug: Tacrolimus
Taken orally or given intravenously for at least 6 months
Other Name: Prograf
Drug: Cyclosporine
Taken orally or given intravenously for at least 6 months
Other Names:
Drug: MMF
Taken orally for about 2 months
Other Names:
|
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.
Eligibility| Ages Eligible for Study: | 18 Years to 72 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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)
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00928018
Locations
| United States, Massachusetts | |
| Dana-Farber Cancer Institute | |
| Boston, Massachusetts, United States, 02115 | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Massachusetts General Hospital
Investigators
| Principal Investigator: | Philippe Armand, MD, PhD | Dana-Farber Cancer Institute |
More Information
No publications provided
| Responsible Party: | Philippe Armand, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00928018 History of Changes |
| Other Study ID Numbers: | 09-073 |
| Study First Received: | June 24, 2009 |
| Last Updated: | January 31, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Dana-Farber Cancer Institute:
|
allogeneic stem cell transplant reduced intensity conditioning graft versus host disease GVHD RIC transplantation |
Additional relevant MeSH terms:
|
Hodgkin Disease Lymphoma Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cyclosporins Cyclosporine Methotrexate Mycophenolic Acid Mycophenolate mofetil Sirolimus |
Everolimus Tacrolimus Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antifungal Agents Anti-Infective Agents Therapeutic Uses Dermatologic Agents Antirheumatic Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents |
ClinicalTrials.gov processed this record on May 22, 2013