Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies
This phase II trial studies how well donor atorvastatin treatment works in preventing severe graft-versus-host disease (GVHD) after nonmyeloablative peripheral blood stem cell (PBSC) transplant in patients with hematological malignancies. Giving low doses of chemotherapy, such as fludarabine phosphate, before a donor PBSC transplantation slows the growth of cancer cells and may also prevent the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also cause an immune response against the body's normal cells (GVHD). Giving atorvastatin to the donor before transplant may prevent severe GVHD.
Adult Acute Lymphoblastic Leukemia
Adult Acute Myeloid Leukemia
Adult Diffuse Large B-Cell Lymphoma
Aggressive Non-Hodgkin Lymphoma
Childhood Acute Lymphoblastic Leukemia
Childhood Acute Myeloid Leukemia
Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Childhood Diffuse Large B -Cell Lymphoma
DS Stage I Plasma Cell Myeloma
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Stage I Adult Hodgkin Lymphoma
Stage I Aggressive Adult Non-Hodgkin Lymphoma
Stage I Childhood Hodgkin Lymphoma
Stage I Chronic Lymphocytic Leukemia
Stage I Diffuse Large B-Cell Lymphoma
Stage I Mantle Cell Lymphoma
Stage I Small Lymphocytic Lymphoma
Stage II Adult Hodgkin Lymphoma
Stage II Childhood Hodgkin Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage II Contiguous Adult Aggressive Non-Hodgkin Lymphoma
Stage II Contiguous Mantle Cell Lymphoma
Stage II Diffuse Large B-Cell Lymphoma
Stage II Non-Contiguous Aggressive Adult Non-Hodgkin Lymphoma
Stage II Non-Contiguous Mantle Cell Lymphoma
Stage II Small Lymphocytic Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Aggressive Adult Non-Hodgkin Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Diffuse Large B-Cell Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Aggressive Adult Non-Hodgkin Lymphoma
Stage IV Childhood Hodgkin Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Diffuse Large B-Cell Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Small Lymphocytic Lymphoma
T-Cell Prolymphocytic Leukemia
Drug: Atorvastatin Calcium
Drug: Fludarabine Phosphate
Radiation: Total-Body Irradiation
Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Mycophenolate Mofetil
Procedure: Peripheral Blood Stem Cell Transplantation
Other: Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Donor Statin Treatment for Prevention of Severe Acute GVHD After Nonmyeloablative Hematopoietic Cell Transplantation|
- Proportion of patients who develop grade 3-4 acute GVHD after transplant [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]The cumulative incidence of this endpoint in patients prepared with nonmyeloablative conditioning regimens after HCT from HLA-matched related donors, and with 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.
- Grades II-IV acute GVHD [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]Assessed with the use of cumulative incidence plots.
- Proportion of patients requiring secondary systemic immunosuppressive therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]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.
- Chronic extensive GVHD [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]Assessed with the use of cumulative incidence plots. Patients will be evaluated for chronic GVHD as described in the NIH consensus project guidelines. Graft failure, recurrent malignancy and death without GVHD are considered to be competing risks for GVHD.
- Recurrent or progressive malignancy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]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.
- Non-relapse mortality [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Defined as death in the absence of recurrent or progressive malignancy after HCT. Assessed with the use of cumulative incidence plots.
- Disease-free survival [ Time Frame: At 1 year after transplant ] [ Designated as safety issue: No ]Evaluated as Kaplan-Meier estimates.
- Overall survival [ Time Frame: At 1 year after transplant ] [ Designated as safety issue: No ]Evaluated as Kaplan-Meier estimates.
- Proportion of donors who have to discontinue atorvastatin because of toxicity [ Time Frame: Prior to stem cell collection ] [ Designated as safety issue: Yes ]The number of donors who prematurely discontinue atorvastatin therapy and the reasons for discontinuation will be described.
|Study Start Date:||September 2012|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Prevention (donor statin treatment)
See Detailed Description
Drug: Atorvastatin Calcium
Other Names:Drug: Fludarabine Phosphate
Other Names:Radiation: Total-Body Irradiation
Other Names:Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Undergo nonmyeloablative allogeneic PBSC transplant
Other Names:Drug: Cyclosporine
Other Names:Drug: Mycophenolate Mofetil
Given PO or IV
Other Names:Procedure: Peripheral Blood Stem Cell Transplantation
Undergo nonmyeloablative allogeneic PBSC transplant
Other Names:Other: Laboratory Biomarker Analysis
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01527045
|United States, Colorado|
|Presbyterian - Saint Lukes Medical Center - Health One||Recruiting|
|Denver, Colorado, United States, 80218|
|Contact: Richard A. Nash 720-754-4800|
|Principal Investigator: Richard A. Nash|
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Marco B. Mielcarek 206-667-2827|
|Principal Investigator: Marco B. Mielcarek|
|Principal Investigator:||Marco Mielcarek||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|