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.
PRIMARY OBJECTIVES: I. To assess whether 2 weeks of donor statin treatment reduces the risk of severe acute GVHD. SECONDARY OBJECTIVES: I. To assess whether 2 weeks of statin treatment of normal PBSC donors is feasible, tolerable and safe. OUTLINE: 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
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
47
Given PO
Given PO
Given IV
Correlative studies
Given PO or IV
Undergo nonmyeloablative allogeneic PBSC transplant
Undergo nonmyeloablative allogeneic PBSC transplant
Undergo TBI
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD) Post-transplant
Number of patients who developed acute GVHD post allogeneic transplant. aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Time frame: 100 days post-transplant
Number of Patients With Grades II-IV Acute Graft-versus-host-disease (GVHD)
Number of patients who developed acute GVHD post allogeneic transplant. aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Time frame: 100 days post-transplant
Number of Patients Requiring Secondary Systemic Immunosuppressive Therapy
Number of patients requiring systemic immunosuppressive therapy other than those used for prophylaxis and initial therapy.
Time frame: 1 Year post-transplant
Number of Patients With Chronic Extensive GVHD
Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD. Patients were evaluated as described in the National Institutes of Health (NIH) consensus project guidelines.
Time frame: 1 Year post-transplant
Number of Patients With Recurrent or Progressive Malignancy
CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever greater than 38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes \>20%. AML, ALL, MDS \>5% marrow blasts by morphologic or flow cytometric, or appearance of extramedullary disease. CLL ≥1 of: Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL \>25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.
Time frame: 1 Year post-transplant
Number of Non-relapse Mortalities
Number of patients who died without relapsed/progressive disease.
Time frame: 1 Year post-transplant
Number of Patients Surviving Overall
Number of patients surviving overall post-transplant
Time frame: 1 Year post-transplant
Number of Donors Discontinuing Atorvastatin Due to Toxicity
The number of donors who prematurely discontinue atorvastatin therapy due to toxicity. Donors will be assessed for the following events: * Musculoskeletal and connective tissue disorders: grade 2-5 * Hepatobiliary disorders: grade 2-5 * Other unexpected events thought related to the use of atorvastatin; grade 2-5 In cases where the NCI criteria do not apply, intensity will be defined as: * Mild: awareness of symptom or sign, but easily tolerated * Moderate: discomfort is enough to cause interference with normal activities * Severe: inability to perform normal daily activities * Life threatening: immediate risk of death from the reaction as it occurred
Time frame: Prior to stem cell collection
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