Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation

This study is currently recruiting participants.
Verified March 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01525407
First received: January 31, 2012
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This clinical trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening


Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Myelodysplastic Syndromes
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
de Novo Myelodysplastic Syndromes
Disseminated Neuroblastoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
High Risk Metastatic Gestational Trophoblastic Tumor
Juvenile Myelomonocytic Leukemia
Low Risk Metastatic Gestational Trophoblastic Tumor
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Plasma Cell Neoplasm
Previously Treated Childhood Rhabdomyosarcoma
Previously Treated Myelodysplastic Syndromes
Primary Myelofibrosis
Prolymphocytic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Gestational Trophoblastic Tumor
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Malignant Testicular Germ Cell Tumor
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Neuroblastoma
Recurrent Ovarian Epithelial Cancer
Recurrent Ovarian Germ Cell Tumor
Recurrent Small Lymphocytic Lymphoma
Recurrent Wilms Tumor and Other Childhood Kidney Tumors
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Splenic Marginal Zone Lymphoma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage II Ovarian Epithelial Cancer
Stage II Ovarian Germ Cell Tumor
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage III Childhood Large Cell Lymphoma
Stage III Childhood Lymphoblastic Lymphoma
Stage III Childhood Small Noncleaved Cell Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Malignant Testicular Germ Cell Tumor
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Ovarian Epithelial Cancer
Stage III Ovarian Germ Cell Tumor
Stage III Small Lymphocytic Lymphoma
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Breast Cancer
Stage IV Childhood Hodgkin Lymphoma
Stage IV Childhood Large Cell Lymphoma
Stage IV Childhood Lymphoblastic Lymphoma
Stage IV Childhood Small Noncleaved Cell Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Ovarian Epithelial Cancer
Stage IV Ovarian Germ Cell Tumor
Stage IV Small Lymphocytic Lymphoma
Drug: atorvastatin calcium
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Donor Statin Treatment for Prevention of Severe Acute GVHD After Myeloablative Hematopoietic Cell Transplantation

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: Ovarian Epithelial Cancer Leukemia, Myeloid Chronic Myeloid Leukemia Myelodysplastic Syndromes Lymphoma, Small Cleaved-cell, Diffuse Multiple Myeloma Chronic Myeloproliferative Disorders Acute Lymphoblastic Leukemia Testicular Cancer Hodgkin Lymphoma Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Homologous Wasting Disease Myelodysplastic/myeloproliferative Disease Neuroblastoma Acute Myeloid Leukemia, Adult Follicular Lymphoma Hodgkin Lymphoma, Childhood B-cell Lymphomas Myelofibrosis Juvenile Myelomonocytic Leukemia Burkitt Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoblastic Lymphoma Small Non-cleaved Cell Lymphoma Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic Kidney Cancer Renal Cancer Chronic Myelomonocytic Leukemia Acute Lymphoblastic Leukemia, Childhood Chronic Neutrophilic Leukemia Wilms' Tumor Hypereosinophilic Syndrome Acute Myeloid Leukemia, Childhood Acute Graft Versus Host Disease Mantle Cell Lymphoma Cutaneous T-cell Lymphoma Gestational Trophoblastic Tumor Ovarian Germ Cell Tumor Hairy Cell Leukemia Mycosis Fungoides Sezary Syndrome Anaplastic Plasmacytoma Germinoma Ovarian Cancer Neuroepithelioma Malignant Mesenchymal Tumor Soft Tissue Sarcoma
U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Grade 3-4 acute GVHD [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    A reduction in the cumulative incidence of acute GVHD from 15% to < 5% would represent a reasonable goal after hematopoietic cell transplant (HCT) with filgrastim (G-CSF)-mobilized blood cells and constitute study success.


Secondary Outcome Measures:
  • Grades II-IV acute and chronic GVHD [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Proportion of patients requiring secondary systemic immunosuppressive therapy [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Chronic extensive GVHD [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    Evaluated for chronic GVHD as described in the NIH consensus project guidelines.

  • Recurrent or progressive malignancy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Non-relapse mortality [ Time Frame: Day 100 and at 1 year after HCT ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Disease-free survival [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]
    Evaluated as Kaplan-Meier estimate.

  • Overall survival [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]
    Determined and presented as Kaplan-Meier estimates.

  • Proportion of donors who have to discontinue atorvastatin because of toxicity [ Time Frame: Up to stem cell collection ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: May 2012
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Supportive care (donor statin treatment)
Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.
Drug: atorvastatin calcium
Given PO
Other Names:
  • CI-981
  • Lipitor
Procedure: peripheral blood stem cell transplantation
Undergo myeloablative allogeneic PBSC transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo myeloablative allogeneic PBSC transplant

Detailed Description:

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:

Donors receive atorvastatin orally (PO) beginning on day -14 and continuing until the last day of stem cell collection.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Human leukocyte antigen (HLA)-identical sibling donor
  • Myeloablative preparative regimen (i.e., >= TBI 12.0 Gy, >= busulfan (BU) 8.0 mg/kg PO, >= BU 6.4 mg/kg intravenously (IV), >= treosulfan 42 g/m^2 IV) according to investigational study or standard treatment plan
  • Transplantation of PBSC
  • Cyclosporine (CSP)-based postgrafting immunosuppression
  • Willingness to give informed consent
  • DONOR: Age >= 18 years
  • DONOR: HLA genotypically identical sibling
  • DONOR: Willingness to give informed consent

Exclusion Criteria:

  • Nonmyeloablative 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
  • DONOR: Age < 18 years
  • DONOR: Active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] levels > 2 times the 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 cytochrome P450 (CYP) 3A4 (i.e. clarithromycin, erythromycin, protease inhibitors, azole antifungals)
  • DONOR: Current use of statin drug
  • DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01525407

Locations
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         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Marco Mielcarek Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01525407     History of Changes
Other Study ID Numbers: 2545.00, NCI-2011-03827, R01HL108307
Study First Received: January 31, 2012
Last Updated: March 17, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Chronic
Leukemia, Neutrophilic, Chronic
Leukemia, Prolymphocytic
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Juvenile
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, B-Cell
Congenital Abnormalities
Primary Myelofibrosis
Blast Crisis
Breast Neoplasms
Burkitt Lymphoma
Neoplasms
Graft vs Host Disease
Hodgkin Disease
Kidney Neoplasms
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Multiple Myeloma

ClinicalTrials.gov processed this record on April 14, 2014