Study of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Progeria
| Status: | Enrolling by invitation |
|---|---|
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/20/2018 |
| Start Date: | August 2009 |
| End Date: | July 2020 |
An Open Label Phase II Trial of Zoledronic Acid, Pravastatin, and Lonafarnib for Patients With Hutchinson-Gilford Progeria Syndrome(HGPS) and Progeroid Laminopathies
Hutchinson-Gilford Progeria Syndrome (Progeria) is a rare autosomal disease that results in
premature death at a median age of 13 years due to cardiovascular and cerebralvascular
compromise. The mutation for this disease has been identified and results in a mutant form of
lamin A that cannot be de-farnesylated. This study evaluates the combination of pravastain (a
statin), lonafarnib (a farnesyltransferase inhibitor) and zoledronic acid (a bisphosphonate)
in an open label phase II efficacy trial in children with Progeria. These agents all target
farnesylation pathways at different points. Patients with genetically confirmed progeria will
be eligible for this protocol. Treatment will be initiated for 24 months duration. Clinical
and biologic parameters will be examined to assess response.
premature death at a median age of 13 years due to cardiovascular and cerebralvascular
compromise. The mutation for this disease has been identified and results in a mutant form of
lamin A that cannot be de-farnesylated. This study evaluates the combination of pravastain (a
statin), lonafarnib (a farnesyltransferase inhibitor) and zoledronic acid (a bisphosphonate)
in an open label phase II efficacy trial in children with Progeria. These agents all target
farnesylation pathways at different points. Patients with genetically confirmed progeria will
be eligible for this protocol. Treatment will be initiated for 24 months duration. Clinical
and biologic parameters will be examined to assess response.
Inclusion Criteria:
- Genetic Diagnosis: All patients must have confirmatory mutational analysis showing
mutation in the lamin A gene.
- Clinical Diagnosis: Patients must display clinical signs of progeria as per the
clinical trial team.
- Travel: Patients must be willing and able to come to Boston for appropriate studies
and examinations at initiation of study and at months 6, 12, 18 and 24 on study.
- Patient must have adequate organ and marrow function as defined by the following
parameters:
- Blood: APC (ANC + bands + monocytes = APC) > 1,000/microliters, Platelets >
75,000/microliters (transfusion independent); Hemoglobin >9g/dl.
- Renal: creatinine Less than or equal 1.5 times normal for age or GFR > 70
ml/min/1.73m2.
- Hepatic: bilirubin Less than or equal to 1.5 x upper limit of normal for age; SGPT
(ALT) < and SGOT (AST) < 5 x normal range for age.
- PT/PTT: PT/PTT < 120% upper limit of normal OR PI approval
- No overt renal, hepatic, pulmonary disease or immune dysfunction.
- 25-hydroxyvitamin D ≥ 20 ng/ml within 4 weeks of bisphosphonate infusion.
- Signed informed consent according to institutional guidelines must be obtained and
patient must begin therapy within twenty eight (28) days.
Exclusion Criteria:
- Other than the drugs used in this protocol, 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 pregnant or 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.
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