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

NCT01491958 | Completed Phase 2 Results DMC

• 2 other identifiers: OSU-11004NCI-2011-03590
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome

Keywords

Leukemia; AML; ALL; MDS

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Grades II to IV aGVHD at Day +100 of Atorvastatin Administration

  The incidence of grades II to IV aGVHD at day +100 of atorvastatin administration. The grading of aGVHD and cGVHD were done using the Consensus Conference criteria.

  Up through day 100 following transplant

Secondary Outcomes (4)

• Safety of Atorvastatin in Transplant Recipients in Terms of Adverse Events and Toxicities.

  Patients: Baseline, weekly for 9 weeks and then on days 84, 91-100, 180 and 365. Donors: at apheresis and then 30 days later.

• Time to Neutrophil and Platelet Engraftment

  weekly for 12 weeks, 100 days, 6 months, and 12 months

• Percentage of Patients With Chronic Graft Versus Host Disease (cGVHD)

  up 1 year post transplant

• Non Relapse Mortality (NRM) at One Year

  up to 12 months post transplant

Study Arms (2)

Donor

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.

Drug: atorvastatin

Patient

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.

Drug: atorvastatin; Drug: Tacrolimus; Drug: methotrexate

Interventions

atorvastatin DRUG

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.

Also known as: Lipitor

Donor; Patient

Tacrolimus DRUG

beginning on Day -2 through approximately Day +180 (that is, approximately 6 months after Day 0)

Also known as: Prograf

Patient

methotrexate DRUG

Day +1, +3, and +6 and +11

Also known as: Amethopterin, MTX

Patient

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Links

• Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia

Interventions

Atorvastatin; Tacrolimus; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Organic Chemicals; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Yvonne Efebera, M.D
• Organization: The Ohio State University Comprehensive Cancer Center

Yvonne.Efebera@osumc.edu

614-293-3196

Study Officials

• Yvonne Efebera, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 9, 2011
• First Posted: December 14, 2011
• Study Start: December 10, 2011
• Primary Completion: January 1, 2014
• Study Completion: June 27, 2016
• Last Updated: January 23, 2018
• Results First Posted: January 23, 2018

Record last verified: 2018-01

Locations

US (1)