Overview

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

Status:
Completed
Trial end date:
2009-04-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Boston Children's Hospital
Boston Children’s Hospital
Collaborators:
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Schering-Plough
Treatments:
Diphosphonates
Lonafarnib
Pravastatin
Zoledronic Acid
Criteria
Inclusion Criteria:

- Genetic Diagnosis: All patients must have confirmatory mutational analysis showing
mutation in the lamin A gene.

- Patients must display clinical signs of progeria as per the clinical trial team.

- Patients must be willing and able to come to Boston for appropriate studies and
examinations at initiation of study and at week 4 of study.

- Patient must have adequate organ and marrow function as defined by study parameters

Exclusion Criteria:

- Other than the drugs used in this protocol, other drugs targeted to treat Progeria are
excluded. Drugs to treat symptoms of Progeria are permitted.

- Patients must not be taking medications that significantly affect the metabolism of
lonafarnib at the time they start lonafarnib.

- Patient must have no uncontrolled infection.

- Subjects who have known or suspected hypersensitivity to any of the excipients
included in the formulation should not be treated.

- Patients must not be pregnancy of breast-feeding. Female patients of childbearing
potential must have negative serum or urine pregnancy test. Male and female patients
of reproductive potential must agree to use a medically accepted form of birth control
while on study and up to 10 weeks after treatment. It is permissible for female
patients to take oral contraceptives or other hormonal methods while receiving
treatment with lonafarnib.