Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies
Condition: 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
MeSH terms: Lymphoma; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Waldenstrom Macroglobulinemia; Multiple Myeloma; Leukemia, Prolymphocytic; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Recurrence; Aggression
Intervention: Atorvastatin Calcium; Cyclosporine; Fludarabine Phosphate; Laboratory Biomarker Analysis; Mycophenolate Mofetil; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Peripheral Blood Stem Cell Transplantation; Total-Body Irradiation
Intervention description: Given PO; Given PO; Given IV; Correlative studies; Given PO or IV; Undergo nonmyeloablative allogeneic PBSC transplant; Undergo nonmyeloablative allogeneic PBSC transplant; Undergo TBI
Intervention MeSH terms: Calcium, Dietary; Cyclosporine; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Atorvastatin; Calcium; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

        IF PROTOCOL 2546 SERVES AS AN ADJUNCT PROTOCOL, THE PATIENTS ONLY NEEDS TO MEET INCLUSION
        CRITERIA 1 THROUGH 5A

          -  Availability of human leukocyte antigen (HLA)-identical sibling donor

          -  Transplantation with PBSC

          -  CSP-based postgrafting immunosuppression

          -  Willingness to give informed consent

          -  Patient is enrolled on an investigational nonmyeloablative HCT protocol or a
             nonmyeloablative treatment plan with postgrafting CSP that does not use acute GVHD as
             its primary endpoint (protocol 2546 serves as adjunct protocol); OR

          -  Patient is not enrolled on an investigational nonmyeloablative HCT protocol, in which
             case protocol 2546 serves as an independent primary treatment protocol and the patient
             must meet the following inclusion and exclusion criteria:

          -  Patients must have a hematologic malignancy treatable by nonmyeloablative HCT; the
             following diseases will be permitted although other diagnoses can be considered if
             approved by Patient Care Conference (PCC) and the principal investigator:

          -  Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large
             B-cell NHL - not eligible for autologous HCT, not eligible for high-dose allogeneic
             HCT, or after failed autologous HCT

          -  Mantle-cell NHL - may be treated in first complete remission (CR); (diagnostic lumbar
             puncture [LP] required pre-transplant)

          -  Low grade NHL - with < 6 month duration of CR between courses of conventional therapy

          -  Chronic lymphocytic leukemia (CLL) - must have either:

               -  Failed to meet National Cancer Institute (NCI) Working Group criteria for
                  complete or partial response after therapy with a regimen containing fludarabine
                  phosphate (FLU) (or another nucleoside analog) or experience disease relapse
                  within 12 months after completing therapy with a regimen containing FLU (or
                  another nucleoside analog)

               -  Failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any
                  time point; or

               -  Have "17p deletion" cytogenetic abnormality; patients should have received
                  induction chemotherapy but could be transplanted in 1st CR

               -  Patients with a diagnosis of CLL (or small lymphocytic lymphoma) that progresses
                  to prolymphocytic leukemia (PLL); or

               -  Patients with T-cell CLL or PLL

          -  Hodgkin lymphoma - must have received and failed frontline therapy

          -  Multiple myeloma - must have received prior chemotherapy; consolidation of
             chemotherapy by autografting prior to nonmyeloablative HCT is permitted

          -  Acute myeloid leukemia (AML) - must have < 5% marrow blasts at the time of transplant

          -  Acute lymphocytic leukemia (ALL) - must have < 5% marrow blasts at the time of
             transplant

          -  Chronic myeloid leukemia (CML) - Patients will be accepted if they have shown
             intolerance to tyrosine kinase inhibitors or are beyond first chronic phase (CP1) and
             if they have received previous myelosuppressive chemotherapy or HCT, and have < 5%
             marrow blasts at time of transplant

          -  Myelodysplasia (MDS)/myeloproliferative syndrome (MPS) - Patients must have < 5%
             marrow blasts at time of transplant

          -  Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy

          -  Patients < 12 years of age must be approved by the principal investigator and by a
             relevant patient review committee, such as the Fred Hutchinson Cancer Research Center
             (FHCRC) Patient Care Conference (PCC)

          -  Patients must have either relapsed after previous high-dose chemotherapy and
             autologous or allogeneic HCT, or else be ineligible for such an approach due to age,
             failure to mobilize sufficient hematopoietic stem cells, medical comorbidities, or
             patient refusal

          -  Patients who refuse to be treated on a conventional autologous or allogeneic HCT
             protocol

          -  DONOR: Age >= 18 years

          -  DONOR: HLA genotypically identical sibling

          -  DONOR: Willingness to give informed consent

        Exclusion Criteria:

        IF PROTOCOL 2546 SERVES AS AN ADJUNCT PROTOCOL, THE PATIENT ONLY NEEDS TO MEET EXCLUSION
        CRITERIA 1 THROUGH 3

          -  Myeloablative preparative regimen

          -  Participation in an investigational study that has acute GVHD as the primary endpoint

          -  The allogeneic PBSC donor has a contraindication to statin treatment

          -  Patients eligible for and willing to receive potentially curative high-dose
             chemotherapy and autologous HCT

          -  Cardiac ejection fraction < 30% on multi gated acquisition scan (MUGA) scan or cardiac
             echocardiogram (echo) or active symptomatic coronary artery disease; patients with
             cardiac disease should be evaluated with appropriate cardiac studies and/or cardiology
             consultation as clinically indicated

          -  Corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 40% of
             predicted, total lung capacity (TLC) < 30% of predicted, forced expiratory volume in
             one second (FEV1) < 30% of predicted, or receiving continuous supplementary oxygen

          -  Patients with clinical or laboratory evidence of liver disease should be evaluated in
             conjunction with the gastrointestinal (GI) consult service for the cause of the liver
             disease, its clinical severity, and the degree of portal hypertension; patients will
             be excluded if they are found to have fulminant liver failure, cirrhosis of the liver
             with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis,
             esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy,
             refractory ascites related to portal hypertension, bacterial or fungal liver abscess,
             chronic viral hepatitis with total serum bilirubin > 3mg/dl, or actively symptomatic
             biliary disease

          -  Patients with renal failure are eligible; however, patients with pre-existing renal
             insufficiency will likely have further compromise in renal function and may require
             dialysis

          -  Patients who are seropositive for human immunodeficiency virus (HIV)

          -  Women who are pregnant or breast-feeding

          -  Fertile men or women unwilling to use contraception during HCT and for 12 months
             afterward

          -  Patients with active non-hematological malignancies (except non-melanoma skin cancers)
             or those with non-hematological malignancies (except non-melanoma skin cancers) who
             have been rendered with no evidence of disease, but have a greater than 20% chance of
             having disease recurrence within 5 years; this exclusion does not apply to patients
             with non-hematologic malignancies that do not require therapy

          -  Karnofsky score < 60 for adult patients

          -  Lansky-play performance score < 50 for pediatric patients

          -  Patients with fungal pneumonia with radiological progression after receipt of
             amphotericin formulation or mold-active azoles for greater than 1 month

          -  DONOR: Age < 18 years

          -  DONOR: History of liver disease; a donor with a history of liver disease would be
             eligible if the serum alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) are < 2 times upper limit of normal (ULN)

          -  DONOR: History of myopathy

          -  DONOR: Hypersensitivity to atorvastatin

          -  DONOR: Pregnancy

          -  DONOR: Nursing mother

          -  DONOR: Current serious systemic illness

          -  DONOR: Concurrent treatment with strong inhibitors of hepatic CYP 3A4 (i.e.
             clarithromycin, erythromycin, protease inhibitors, azole antifungals)

          -  DONOR: Failure to meet local criteria for stem cell donation

          -  DONOR: Total creatinine kinase > 2 times the ULN