Phase I/II Trial of Everolimus in Combination With Lonafarnib in Progeria
This is a phase I/II dose-escalation trial of everolimus in combination with lonafarnib in Hutchinson-Gilford Progeria Syndrome (HGPS) and progeroid laminopathies (henceforth progeria). The study will be conducted at a single clinical site utilizing the Clinical and Translational Study Unit (CTSU) at Boston Children's Hospital. Lonafarnib will be administered at doses previously established in the pediatric population and in this population of progeria subjects. This study will first determine the dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) of everolimus when administered in combination with lonafarnib. It will then determine the efficacy of everolimus when administered at its MTD in combination with lonafarnib for disease in progeria.
• 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.