Safety & Efficacy of Atorvastatin for Prophylaxis of Acute Graft Versus Host Disease in Patients With Hematological Malignancies HLA- Donor Hematopoietic Stem Cell Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Yvonne Efebera, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01491958
First received: December 9, 2011
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

Phase II trial evaluating the safety & efficacy of Atorvastatin for prophylaxis of Acute Graft Versus Host Disease (GVHD) in patients with hematological malignances undergoing human leukocyte antigen (HLA)-Matched Related Donor Hematopoietic Stem Cell Transplant (HSCT).


Condition Intervention Phase
Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Drug: atorvastatin
Drug: Tacrolimus
Drug: methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Phase II Trial Evaluating the Safety and Efficacy of Atorvastatin for the Prophylaxis of Acute Graft Versus Host Disease(GVHD) in Patients With Hematological Malignancies Undergoing HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation (HSCT)

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Efficacy of atorvastatin added to standard GVHD prophylaxis regimen with tacrolimus and methotrexate, in reducing the incidence of grade II-IV acute GVHD. [ Time Frame: Up through day 100 following transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety of atorvastatin in healthy sibling donors and transplant recipients in terms of adverse events and toxicities. [ Time Frame: Patients: Baseline, weekly for 9 weeks and then on days 84, 91-100, 180 and 365. Donors: at apheresis and then 30 days later. ] [ Designated as safety issue: Yes ]
  • Neutrophil and platelet engraftment [ Time Frame: weekly for 12 weeks, 100 days, 6 months, and 12 months ] [ Designated as safety issue: No ]
  • chronic GVHD [ Time Frame: up through day 100 post transplant ] [ Designated as safety issue: No ]
  • NRM [ Time Frame: up to 12 months post transplant ] [ Designated as safety issue: No ]
    NRM will be defined as death from any cause other than relapse.


Estimated Enrollment: 41
Study Start Date: December 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Donor
Related donors will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines. Peripheral blood stem cells will not be manipulated or T-depleted prior to administration.
Drug: atorvastatin

donors-will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines.

Patients-will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first.

Other Name: Lipitor
Experimental: Patient
Patients will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first. Standard post transplant care will be administered.
Drug: atorvastatin

donors-will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines.

Patients-will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first.

Other Name: Lipitor
Drug: Tacrolimus
beginning on Day -2 through approximately Day +180 (that is, approximately 6 months after Day 0)
Other Name: Prograf
Drug: methotrexate
Day +1, +3, and +6 and +11
Other Names:
  • Amethopterin
  • MTX

Detailed Description:

The study is a single-arm phase II single institutional trial evaluating the safety and efficacy of atorvastatin for the prophylaxis of acute GVHD in patients with hematological malignancies undergoing HLA matched related donor HSCT. This study will explore a two-pronged acute GVHD prophylaxis strategy, consisting of pre-treating consenting related donors with atorvastatin before stem cell mobilization and collection, followed by atorvastatin plus methotrexate/tacrolimus-based GVHD prophylaxis in transplant recipient patients.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Donor Eligibility Criteria

  • The donor must be at least 18 years of age, and willing/able to provide informed consent. Complete medication list will be reviewed for potential negative interaction with atorvastatin.
  • The donor must be an HLA-matched sibling or relative.
  • Syngeneic donors are not eligible.
  • Female donors of child-bearing potential should have a negative pregnancy test, and must not be breast feeding.
  • Bilirubin, AST and ALT must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
  • Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
  • Adequate cardiac function with no history of congestive heart failure, uncontrolled atrial fibrillation or ventricular tachyarrhythmias.

Patient Eligibility Criteria

  • Have hematologic malignancy requiring allogeneic HSCT, have adequate organ function, a serologic (or higher resolution) 6/6 class I human leukocyte antigen (HLA)-A and B and molecular class II DRB1 matched related donor, and are able to give informed consent.
  • Patients > 18 and ≤ 65 years with comorbidity score ≤ 3 will be eligible for myeloablative conditioning (MAC), while patients > 65 years of age, those with previous history of autologous transplantation, or high comorbidity index (>3) will be eligible for reduced intensity conditioning (RIC) transplantation .
  • All patients must have at least one 6/6 HLA-matched sibling donor.
  • Patient must provide informed consent
  • Patients must have left ventricular ejection fraction > 30%, no uncontrolled arrhythmias or New York Heart Association class III-IV heart failure.
  • Bilirubin must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be <2 x normal; and absence of hepatic fibrosis/cirrhosis.
  • Serum creatinine clearance of ≥40% of normal calculated by Cockcroft-Gault equation.
  • Forced expiratory volume in one second (FEV1)and diffusion capacity; corrected for hemoglobin(DLCO) ≥ 50% and 40% of predicted respectively.
  • Karnofsky performance status > 70.
  • A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
  • No HIV infection. Patients with immune dysfunction are at a significantly higher risk of toxicities from intensive immunosuppressive therapies.
  • No evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
  • No active alcohol or substance abuse within 6 months of study entry.
  • Prior allogeneic transplant is acceptable.
  • No history of intolerance or allergic reactions with atorvastatin or other statins.
  • Patients who have previously been taking atorvastatin or any other statin will be eligible as long as there is no contraindication to switch to atorvastatin 40mg/day in the opinion of the treating physician.

Exclusion Criteria:

  • Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.
  • Patients receiving another investigational drug are not eligible unless cleared by Principal Investigator. Patients with prior malignancies except resected basal cell carcinoma, treated carcinoma in-situ, or other hematologic diseases for which allogeneic HSCT is a treatment strategy, are not eligible. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Principal Investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01491958

Locations
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Ohio State University Comprehensive Cancer Center
Investigators
Principal Investigator: Yvonne Efebera, MD Ohio State University
  More Information

Additional Information:
No publications provided

Responsible Party: Yvonne Efebera, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01491958     History of Changes
Other Study ID Numbers: OSU-11004, NCI-2011-03590
Study First Received: December 9, 2011
Last Updated: February 4, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio State University Comprehensive Cancer Center:
Leukemia
AML
ALL
MDS

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia
Graft vs Host Disease
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Atorvastatin
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 18, 2014