A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
|Progeria Hutchinson-Gilford Syndrome||Drug: Lonafarnib Drug: Zoledronic Acid Drug: Pravastatin||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Open LabelPrimary Purpose: Treatment
|Official Title:||A Phase II Pilot Study of Zoledronic Acid, Pravastatin, and Lonafarnib (SCH66336) for Patients With Hutchinson-Gilford Progeria Syndrome (HGPS) and Progeroid Laminopathies|
- The Primary Objective of This Study is to Evaluate the Feasibility of Administering Intravenous Zoledronic Acid, Oral Pravastatin and Oral Lonafarnib, to Patients With Progeria for a Minimum of 4 Weeks [ Time Frame: 4 weeks ]Feasibility was assessed by determining the number of participants with adverse events occurring over the course of the 4 week study.
- To Describe Any Acute and Chronic Toxicities Associated With Treating Progeria Patients With the Combination of Zoledronic Acid, Pravastatin and Lonafarnib [ Time Frame: 4 weeks ]Number of participants with acute and chronic toxicities associated with treating progeria patients with the combination of zoledronic acid, pravastatin and lonafarnib
- To Investigate Which Clinical and Laboratory Studies Are Needed to Monitor or Alter Therapy to Prevent Unacceptable Toxicity [ Time Frame: 4 weeks ]The number of participants with abnormal CBC w/diff panel, LFTs, renal functions and lipid panels.
- To Assess the Pharmacokinetics of Lonafarnib in Patients With Progeria. [ Time Frame: 4 weeks ]
- To Assay for the Inhibition of HDJ-2 Farnesylation in Peripheral Blood Leukocytes (PBL) [ Time Frame: 4 weeks ]
- To Obtain Baseline Clinical and Laboratory Data so That Longer-term Measures of Efficacy Will be Achievable if Treatment Continues Beyond the 4-week Feasibility Study Period. [ Time Frame: 4 weeks ]The number of participants from whom baseline clinical and Laboratory data was obtained.
|Study Start Date:||March 2009|
|Study Completion Date:||April 2009|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Experimental: Zoledronic Acid,Pravastatin,and Lonafarnib
Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level.
Other Name: Sarasar, SCH 66336Drug: Zoledronic Acid
Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight.
Other Name: Zometa, ReclastDrug: Pravastatin
Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.
Other Name: Pravachol
Progerias are rare "premature aging" diseases in which children die of severe atherosclerosis leading to strokes and heart attacks. It is a multisystem disease with objective clinical markers for disease progression. These include abnormalities in growth and body composition, bone mineral density, join function, endocrine function, alopecia, and vascular disease. There is currently no therapy proven effective for any of the progressive and deleterious aspects of this disorder.
Progeria is caused by a gene defect in the gene LMNA, coding for the nuclear protein lamin A. Lamin A is normally expressed by most differentiated cells, and requires posttranslational farnesylation to incorporate into the nuclear membrane. This trial proposes to use three agents (zoledronic acid, pravastatin, and lonafarnib) to inhibit farnesylation of abnormal lamin, the disease causing protein in Progeria. The primary objective of this study is to evaluate the feasibility of administering intravenous zoledronic acid, oral pravastatin and oral lonafarnib, to patients wtih Progeria for a minimum of 4 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00879034
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|Study Chair:||Mark W Kieran, MD, PhD||Dana-Farber Cancer Institute; Boston Children's Hospital|