Overview

This trial is active, not recruiting.

Conditions acute myelogenous leukemia, acute lymphocytic leukemia, myelodysplastic syndrome
Treatments atorvastatin, tacrolimus, methotrexate
Phase phase 2
Sponsor Ohio State University Comprehensive Cancer Center
Start date December 2011
End date December 2016
Trial size 41 participants
Trial identifier NCT01491958, NCI-2011-03590, OSU-11004

Summary

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose supportive care
Arm
(Experimental)
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.
atorvastatin Lipitor
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.
(Experimental)
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.
atorvastatin Lipitor
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.
tacrolimus Prograf
beginning on Day -2 through approximately Day +180 (that is, approximately 6 months after Day 0)
methotrexate Amethopterin
Day +1, +3, and +6 and +11

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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.
Neutrophil and platelet engraftment
time frame: weekly for 12 weeks, 100 days, 6 months, and 12 months
chronic GVHD
time frame: up through day 100 post transplant
NRM
time frame: up to 12 months post transplant

Eligibility Criteria

Male or female participants from 18 years up to 75 years old.

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.

Additional Information

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)
Principal investigator Yvonne Efebera, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Ohio State University Comprehensive Cancer Center.