Clinical trial NCT01491958: Safety & Efficacy of Atorvastatin for Prophylaxis of Acute Graft Versus Host Disease in Patients With Hematological Malignancies HLA- Donor Hematopoietic Stem Cell Transplantation
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
Keywords: Leukemia
AML
ALL
MDS
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2011-12-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief 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).

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 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.

Primary outcomes:
measure: Percentage of Participants With Grades II to IV aGVHD at Day +100 of Atorvastatin Administration
timeFrame: Up through day 100 following transplant
Secondary outcomes:
measure: Safety of Atorvastatin in Transplant Recipients in Terms of Adverse Events and Toxicities.
timeFrame: Patients: Baseline, weekly for 9 weeks and then on days 84, 91-100, 180 and 365. Donors: at apheresis and then 30 days later.
measure: Time to Neutrophil and Platelet Engraftment
timeFrame: weekly for 12 weeks, 100 days, 6 months, and 12 months
measure: Percentage of Patients With Chronic Graft Versus Host Disease (cGVHD)
timeFrame: up 1 year post transplant
measure: Non Relapse Mortality (NRM) at One Year
timeFrame: up to 12 months post transplant
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Yvonne Efebera, MD
role: PRINCIPAL_INVESTIGATOR
References: