Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoi... | NCT01665677

NCT01665677

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
WVU 011012	Other Identifier	West Virginia
116837-IRG-09-061-01	Other Grant/Funding Number	American Cancer Society

Status Module

Name	Class
West Virginia University	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Atorvastatin calcium (Lipitor)	Experimental	Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.	Drug: Atorvastatin calcium
Unrelated Donor	Experimental	Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.	Drug: Atorvastatin calcium

Name	Type	Description	Arm Group Labels	Other Names
Atorvastatin calcium	Drug	40 mg PO daily	Atorvastatin calcium (Lipitor) Unrelated Donor

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Matched Related Transplants Who Develop Grade II-IV Acute Graft Versus Host Disease (GVHD).	The number of subjects in the matched sibling cohort who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched unrelated donors are not included in this analysis.	Day 100
Matched Unrelated Donors Transplants Who Develop Grade II-IV Acute GVHD.	The number of subjects in the matched unrelated donor cohort who develop grade II-IV acute GVHD. Acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched related donors are not included in this analysis.	Day 100

Secondary Outcomes

Measure	Description	Time Frame
Matched Related Transplants Who Develop Grade II-IV Chronic GVHD.	The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading I to IV will be according to National Institutes of Health (NIH) Criteria rating progressively intense symptoms involving: skin (asymptomatic to deep sclerosis, impaired mobility, ulceration, or pruritus), oral cavity (asymptomatic to symptoms limiting oral intake), eyes (asymptomatic to severe dry eye, inability to work, or loss of vision due to keratoconjunctivitis), gastrointestinal tract (asymptomatic to significant weight loss [>15%] or esophageal dilation), liver (normal function to bilirubin or enzymes >5 times ULN), lungs (asymptomatic to severe shortness of breath requiring supplemental oxygen), joints and fascia (asymptomatic to contractures with reduced range of motion and limited ability to perform daily care), and genital tract (asymptomatic to strictures and severe pain). Subjects in the matched unrelated donors are not included in this analysis.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with a history of a hematological malignancy or bone marrow failure syndrome suitable for allogeneic stem cell transplantation in the opinion of treating transplant physician.
Patients aged 18-75 years of age are eligible. Patients with age > 18 and ≤ 50 years will be eligible for myeloablative conditioning (MAC), while patients > 50 years of age, or those with previous history of autologous transplantation, high hematopoietic cell transplant comorbidity index (HCT-CI) score (>2), and baseline diagnosis of hodgkin's lymphoma, chronic lymphocytic leukemia and follicular lymphoma will be suitable for reduced intensity conditioning (RIC) transplantation (however intensity of conditioning regimen will remain at the discretion of treating physician).
All patients must have at least one suitable human leukocyte antigen (HLA)-matched sibling or unrelated donor according to transplant center's guidelines (for selection of appropriate sibling donor).
Patient must provide informed consent.
Left ventricular ejection fraction ≥ 40%.
Bilirubin ≤ 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 3 x ULN; and absence of hepatic cirrhosis. For patients with Gilbert's syndrome, bilirubin ≤ 3 x ULN is permitted.
Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
Carbon monoxide diffusing capacity (DLCOcor) corrected for hemoglobin or forced expiratory volume at one second (FEV1) or DL/VA ≥ 40% of predicted (a pulmonary function test).
Karnofsky performance status > 70.
A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
Patients with positive HIV serology are eligible.
Patients who have previously been taking atorvastatin or any other statin drug will be eligible as long as there is no contraindication to switch to atorvastatin (40mg/day) in the opinion of the treating physician.
Method of stem-cell collection from the sibling donor will be at the discretion of the treating physician. Although it is anticipated that majority of sibling donors will undergo Granulocyte colony-stimulating factor(G-CSF) induced stem cell mobilization; however donors undergoing bone marrow harvest or stem cell mobilization with experimental agents (e.g. plerixafor) will remain eligible for the study.

Exclusion Criteria:

Uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
Evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
History of intolerance or allergic reactions with atorvastatin will not be eligible.
Undergoing a T-cell depleted allogeneic transplantation
Receiving conditioning regimens containing anti-thymocyte globulin, and/or campath

Name	Affiliation	Role
Michael Craig, MD	West Virginia University	Principal Investigator
Mehdi Hamadani, MD	Medical College of Wisconsin	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
West Virginia University Hospitals Mary Babb Randolph Cancer Center		Morgantown	West Virginia	26506	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
17234737	Background	Deeg HJ. How I treat refractory acute GVHD. Blood. 2007 May 15;109(10):4119-26. doi: 10.1182/blood-2006-12-041889. Epub 2007 Jan 18.
9746768	Background	Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, Fay JW, Nademanee A, Antin JH, Christiansen NP, van der Jagt R, Herzig RH, Litzow MR, Wolff SN, Longo WL, Petersen FB, Karanes C, Avalos B, Storb R, Buell DN, Maher RM, Fitzsimmons WE, Wingard JR. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998 Oct 1;92(7):2303-14.

Arm/Group Information

ID	Title	Description
FG000	Matched Related Donor	Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin. Atorvastatin calcium: 40 mg PO daily
FG001	Matched Unrelated Donor	Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin. Atorvastatin calcium: 40 mg PO daily

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Atorvastatin Calcium (Lipitor)	Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin. Atorvastatin calcium: 40 mg PO daily

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Matched Related Transplants Who Develop Grade II-IV Acute Graft Versus Host Disease (GVHD).

The number of subjects in the matched sibling cohort who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets. Grade I is mild GVHD involving up to 25% of the subject's skin; Grade II is moderate GVHD. involving 25 to 50% of the subject's skin and can include mild changes in liver and/or mild diarrhea; Grade III is severe GVHD involving over 50% of the subject's skin. Liver involvement is likely as are stomach cramps and diarrhea; and Grade 4 is very severe GvHD. Skin may be blistered and may have broken down in places. Skin may be yellow due to liver injury. Severe diarrhea is common. Subjects in the matched unrelated donors are not included in this analysis.

Posted

Count of Participants

Participants

Day 100

ID	Title	Description
OG000	Matched Related Donor

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Atorvastatin Calcium (Lipitor)	Atorvastatin will be administered at a dose of 40 mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin. Atorvastatin calcium: 40 mg PO daily

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 3, 2014	Nov 30, 2022	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Oct 20, 2014	Nov 30, 2022	ICF_001.pdf

ID	Term
D011758	Pyrroles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds