Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies
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|ClinicalTrials.gov Identifier: NCT01527045|
Recruitment Status : Recruiting
First Posted : February 6, 2012
Last Update Posted : February 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Aggressive Non-Hodgkin Lymphoma Blasts Under 5 Percent of Bone Marrow Nucleated Cells Chronic Lymphocytic Leukemia Loss of Chromosome 17p Myelodysplastic/Myeloproliferative Neoplasm Non-Hodgkin Lymphoma Prolymphocytic Leukemia Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Aggressive Adult Non-Hodgkin Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Chronic Lymphocytic Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Recurrent Diffuse Large B-Cell Lymphoma Recurrent Hodgkin Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent Plasma Cell Myeloma Recurrent Small Lymphocytic Lymphoma Waldenstrom Macroglobulinemia||Drug: Atorvastatin Calcium Drug: Cyclosporine Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Mycophenolate Mofetil Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation Procedure: Peripheral Blood Stem Cell Transplantation Radiation: Total-Body Irradiation||Phase 2|
I. To assess whether 2 weeks of donor statin treatment reduces the risk of severe acute GVHD.
I. To assess whether 2 weeks of statin treatment of normal PBSC donors is feasible, tolerable and safe.
DONOR: Donors receive atorvastatin orally (PO) once daily (QD) beginning on day -14 and continuing until the last day of stem cell collection.
NONMYELOABLATIVE PREPARATIVE REGIMEN: If the patient is enrolled on an investigational nonmyeloablative hematopoietic cell transplant (HCT) protocol or a treatment plan that uses a nonmyeloablative preparative regimen with postgrafting cyclosporine (CSP) that does not use acute GVHD as its primary endpoint, the preparative regimen and immunosuppression after transplant will be according to respective protocol or treatment plan (Protocol 2546 serves as adjunct protocol).
If the patient is not enrolled on an investigational nonmyeloablative HCT protocol or a treatment plan that uses a nonmyeloablative preparative regimen, Protocol 2546 serves as an independent primary treatment protocol. The preparative regimen and immunosuppression after transplant is as follows:
Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 (except for patients who had prior autologous HCT or equivalent high-dose therapy without HCT) and undergo low-dose total body irradiation (TBI) on day 0.
TRANSPLANT: Patients undergo donor PBSC transplant on day 0.
POST-GRAFTING IMMUNOSUPPRESSION: Patients receive CSP PO twice daily (BID) on days -3 to 56 with taper to day 180. Patients also receive mycophenolate mofetil (MMF) PO BID or IV every 12 hours on days 0-27.
After completion of study treatment, patients are followed up at 1 year and then annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Donor Statin Treatment for Prevention of Severe Acute GVHD After Nonmyeloablative Hematopoietic Cell Transplantation|
|Actual Study Start Date :||September 25, 2012|
|Estimated Primary Completion Date :||October 26, 2018|
Experimental: Prevention (donor statin treatment)
See Detailed Description
Drug: Atorvastatin Calcium
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Drug: Mycophenolate Mofetil
Given PO or IV
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo nonmyeloablative allogeneic PBSC transplant
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo nonmyeloablative allogeneic PBSC transplant
Radiation: Total-Body Irradiation
- Proportion of patients who develop grade 3-4 acute graft-versus-host disease (GVHD) after transplant [ Time Frame: Up to day 100 ]The cumulative incidence of this endpoint in patients prepared with nonmyeloablative conditioning regimens after hematopoietic cell transplant (HCT) from human leukocyte antigen (HLA)-matched related donors, and with cyclosporine (CSP)-based immunosuppression is approximately 9%. A reduction in the cumulative incidence of acute GVHD from 9% to < 2% would represent a reasonable goal after nonmyeloablative HCT and constitute study success.
- Chronic extensive GVHD [ Time Frame: Up to day 100 ]Assessed with the use of cumulative incidence plots. Patients will be evaluated for chronic GVHD as described in the National Institutes of Health (NIH) consensus project guidelines. Graft failure, recurrent malignancy and death without GVHD are considered to be competing risks for GVHD.
- Disease-free survival [ Time Frame: At 1 year after transplant ]Evaluated as Kaplan-Meier estimates.
- Grades II-IV acute GVHD [ Time Frame: Up to day 100 ]Assessed with the use of cumulative incidence plots.
- Non-relapse mortality [ Time Frame: Up to 1 year ]Defined as death in the absence of recurrent or progressive malignancy after HCT. Assessed with the use of cumulative incidence plots.
- Overall survival [ Time Frame: At 1 year after transplant ]Evaluated as Kaplan-Meier estimates.
- Proportion of donors who have to discontinue atorvastatin because of toxicity [ Time Frame: Prior to stem cell collection ]The number of donors who prematurely discontinue atorvastatin therapy and the reasons for discontinuation will be described.
- Proportion of patients requiring secondary systemic immunosuppressive therapy [ Time Frame: Up to 4 years ]Assessed with the use of cumulative incidence plots. The need for primary and secondary systemic immunosuppressive treatment with agents other than those used for prophylaxis and initial therapy, the reason for their administration (acute GVHD, chronic GVHD, or other reasons) will be determined.
- Recurrent or progressive malignancy [ Time Frame: Up to 4 years ]Assessed with the use of cumulative incidence plots. Recurrent malignancy will be defined by hematologic criteria. Recurrent malignancy will also be defined as any unplanned medical intervention designed to prevent progression of malignant disease in patients who have molecular, cytogenetic or flow-cytometric evidence of malignant cells after transplantation.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01527045
|United States, Colorado|
|Presbyterian - Saint Lukes Medical Center - Health One||Completed|
|Denver, Colorado, United States, 80218|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Marco Mielcarek 206-667-2827 email@example.com|
|Principal Investigator: Marco Mielcarek|
|Principal Investigator:||Marco Mielcarek||Fred Hutch/University of Washington Cancer Consortium|