| Eligibility |
Inclusion Criteria:
- Genetically-confirmed progeria.
- display clinical signs of progeria as per the clinical trial team.
- currently receiving lonafarnib under protocol 09-06-0298
- have not experienced a grade 3 or 4 toxicity within two months preceding enrollment
- willing and able to come to Boston for appropriate studies and examinations.
- no recent fractures or major surgery (within four weeks)
- Absolute poly count (Absolute neutrophil count + bands + monocytes) >1,000/uL
- platelets >75,000/uL (transfusion independent)
- hemoglobin >9 g/dL
- creatinine = 1.5 times upper limit of normal (ULN) for age or Glomerular filtration
rate (GFR) >70 mL/min/1.73m2
- bilirubin = 1.5x upper limit of normal for age
- SGPT (ALT) < and SGOT (AST) = 2.5x normal range for age
- serum albumin greater than or equal to 2 g/dL
- PT/PTT: INR <1.3 (or <3 on anticoagulants)
- Fasting LDL cholesterol within 1.5x ULN per institutional guidelines (ie, <195 mg/dL
for 2 - 18 years of age, <240 mg/dL for subjects >18 years old)* and Fasting serum
cholesterol <300 mg/dL (<7.75 mmol/L)* and Fasting triglycerides <2.5 ULN (<325 mg/dL
for ages 2 - 18, <400 for ages >18)*
*may be re-evaluated for eligibility after initiation of lipid-lowering therapy
- Signed informed consent according to institutional guidelines must be obtained and
subject must begin therapy within twenty-eight (28) days.
Exclusion Criteria:
- Subjects must not be taking medications that significantly affect the metabolism of
lonafarnib
- Subjects receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Subjects with endocrine deficiencies are allowed to receive
physiologic or stress doses of steroids if necessary. Topical or inhaled steroids are
allowed.
- Subjects who have had a major surgery or significant traumatic injury within 4 weeks
of start of study drug; have not recovered from the side effects of any major surgery
(defined as requiring general anesthesia but excluding a procedure for insertion of
central venous access); or who may require major surgery during the course of the
study.
- 13.2.5 Subjects with an active bleeding diathesis or on oral anti-vitamin K medication
(except low dose coumadin).
- Subjects who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as:
- known severely impaired lung function
- active (acute or chronic) or uncontrolled severe infections.
- liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis.
- History of hepatitis B or hepatitis C
- Other concurrent severe and/or uncontrolled medical disease that could compromise
participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension,
severe infection, severe malnutrition, chronic liver or renal disease, active upper GI
tract ulceration).
- A known history of Human Immunodeficiency Virus (HIV) seropositivity or known
immunodeficiency.
- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of everolimus (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
resection). A nasogastric tube (NG tube) or gastric tube (G tube) is allowed.
- Subjects who have known or suspected hypersensitivity to any of the excipients
included in the formulation should not be treated.
- Subjects must not be pregnant or breast-feeding. Female subjects of childbearing
potential must have negative serum or urine pregnancy test. Sexually active male and
female subjects 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 subjects to take oral contraceptives or other hormonal methods while
receiving treatment with everolimus.
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