Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease (GVHD) Prophylaxis After Reduced Intensity Conditioning (RIC) Hematopoietic Stem Cell Transplantation
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|ClinicalTrials.gov Identifier: NCT00548717|
Recruitment Status : Terminated (First two patients enrolled after trial reopened, developed grade III-IV acute GVHD and subsequently passed away.)
First Posted : October 24, 2007
Results First Posted : October 21, 2014
Last Update Posted : October 21, 2014
|Condition or disease||Intervention/treatment||Phase|
|Graft-vs-Host Disease||Drug: Sirolimus Drug: Mycophenolate mofetil Drug: Bortezomib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Sirolimus, Mycophenolate Mofetil and Bortezomib as Graft-Versus-Host Disease Prophylaxis After Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation|
|Study Start Date :||October 2007|
|Actual Primary Completion Date :||September 2013|
|Actual Study Completion Date :||September 2013|
Sirolimus and Mycophenolate Mofetil as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF)
Other Name: RapamycinDrug: Mycophenolate mofetil
Other Name: Cellcept
Sirolimus, Mycophenolate Mofetil, and Bortezomib as GVHD Prophylaxis Sirolimus (Rapamycin); Mycophenolate Mofetil (MMF) Bortezomib (Velcade) *added with study reopening in 2012
Other Name: RapamycinDrug: Mycophenolate mofetil
Other Name: CellceptDrug: Bortezomib
Other Name: Velcade
- To Determine the Rate of Grade II-IV Acute GVHD When Sirolimus and Mycophenolate Mofetil or Sirolimus, Mycophenolate Mofetil and Bortezomib is Used for GVHD Prophylaxis After Allogeneic Stem Cell Transplantation in Patients With Hematologic Malignancies [ Time Frame: 150 days ]
- Donor Stem Cell Engraftment, Including Donor-host Hematopoietic Chimerism Studies Post Transplant [ Time Frame: 30 days ]Engraftment of donor cells by week 4 after transplantation. Assessment of donor stem cell engraftment will include donor-host hematopoietic chimerism analyses at 4 weeks and every 3 months after transplantation. Chimerism measured from peripheral blood or from bone marrow.
- The Rate of Renal Insufficiency [ Time Frame: 1 year ]
Renal function will be measured weekly after transplant for 4 weeks, at 8 weeks and then at 3 month intervals from transplantation. Sentinel renal events such as the occurrence of thrombotic microangiopathy will be noted.
The rationale for the substitution of mycophenolate mofetil for tacrolimus is to continue to prevent acute GVHD, but minimize renal toxicity after transplantation. We will thus monitor renal toxicity closely in this study. In our previous experience, the rate of grade III‐V renal toxicity by day 100 after transplantation was about 10%. Here, grade III is defined as a creatinine level between 3.1 to 6 times the normal level, grade IV is defined as a creatinine level 6 times or more the normal level, and grade V is defined as a fatality due to renal toxicity.
- To Correlate the Serum Concentrations of Mycophenolate Mofetil and Its Metabolites With Acute GVHD Incidence [ Time Frame: 1 year ]This outcome measure was presented as a comparison between incidence of Grade 0-I aGVHD and Grade II-IV aGVHD across 5 time points (Weeks 1,2,3,8, and 12).
- Incidence of 100 Day Mortality [ Time Frame: 100 days ]
- Incidence of Chronic GVHD [ Time Frame: 1 year ]
Chronic GVHD will be graded according to the modified Seattle criteria. Chronic GVHD divided into limited and extensive and evaluated across the following systems: skin, cutaneous structures, liver, mouth, eyes, esophagus, intestines, lung, musculoskeletal, serous, nervous, urologic, vagina, hematopoietic, and immune.
Localized skin involvement with or without hepatic dysfunction is classified as limited disease.
Generalized skin involvement or limited disease plus eye involvement, oral involvement, hepatic dysfunction with abnormal liver histology, or involvement of any other target organ was classified as extensive disease.
Lee SJ, Vogelsang G, Flowers ME. Chronic graft‐versus‐host disease. Biol Blood Marrow Transplant.
- Overall Survival [ Time Frame: 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00548717
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Principal Investigator:||Corey Cutler, MD||Dana-Farber Cancer Institute|