A Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria

Summary

This is an open label single arm feasibility trial. A combination of two oral agents (pravastatin and lonafarnib) and one intravenous (IV) agent (zoledronic acid) will be administered at doses and schedule currently applied in pediatrics. These agents all target farnesylation pathways at different points. Our goal is to inhibit farnesylation of abnormal lamin, the disease-causing protein in Hutchinson-Gilford Progeria Syndrome and progeroid laminopathies (henceforth "progeria"). The drugs will include the intravenous bisphosphonate zoledronic acid, oral HMG co-reductase inhibitor pravastatin and the oral farnesyltransferase inhibitor (FTI) lonafarnib (SCH 66336). Patients with genetically confirmed progeria will be eligible for this protocol. Treatment will be initiated for 4 weeks duration and may be extended depending on tolerability. This study will assess the feasibility of this treatment regimen in the first 4 weeks. If tolerated for 4 weeks, patients can be treated with this regimen for up to 6 months.

Conditions

• Progeria
• Hutchinson-Gilford Syndrome

Interventions

DRUG

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.

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute

  collaborator OTHER

• Brigham and Women's Hospital

  collaborator OTHER

• Schering-Plough

  collaborator INDUSTRY

• Boston Children's Hospital

  lead OTHER

Principal Investigators

• Mark W Kieran, MD, PhD · Dana-Farber Cancer Institute; Boston Children's Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-03-31

Primary Completion

2009-04-30

Completion

2009-04-30

Countries

• United States

Study Locations