Intervention: Lonafarnib
Trial phase: Phase 2
ATC code: A16AX20
SMILES: NC(=O)N1CCC(CC(=O)N2CCC([C@H]3c4ncc(Br)cc4CCc4cc(Cl)cc(Br)c43)CC2)CC1
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 28
Group description: Lonafarnib (Merck & Co., Inc.) dosing was initiated at 115 mg/m2 and was increased to 150 mg/m2 after an adjustment period of at least 4 mo. Dosage was reduced back to 115 mg/m2 fo patients experiencing drug-related grade 3 or 4 toxicity and also not responding to supportive care. Once dosage was reduced, patients were permitted to increase the dose of lonafarnib. Patients received oral lonafarnib either by capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus (Paddock Laboratories, Inc.) every 12 ± 2 h for a period of 24-29 mo. Patients were monitored for liver, kidney, and hematological toxicity each month for the first 3 mo by their local physicians and every 4 mo in Boston for the duration of the study. Adverse events were monitored and recorded throughout the study.
Eligibility criteria:
Inclusion Criteria:

All patients must have confirmatory mutational analysis showing G608G mutation in the lamin A gene.
Patients with progeroid laminopathies, showing clinical signs of Progeria but with other confirmed mutations in LMNA will be eligible for therapy. This population will be analyzed separately from those with the classical mutations.
Patients must be willing and able to come to Boston for appropriate studies and examinations approximately once every 4 months.
Patients must have a minimum of one year of weight data available, with five data points or more, each separated by one month or more over a one year period and approval by the study team.
APC (ANC + bands + monocytes = APC) > 1,000/ml, Platelets > 75,000/ml (transfusion independent); Hemoglobin >9g/dl.
creatinine less than or equal to 1.5 times normal for age or GFR > 70 ml/min/1.73m2.
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 < 120% upper limit of normal OR PI approval.
No overt renal, hepatic, pulmonary disease or immune dysfunction.
Patients taking growth hormone when entering the study must have pretreatment weight measures while on growth hormone which are specified above. In addition, patients must remain on growth hormone treatment for the duration of the present clinical trial. Patients entering the trial not on growth hormone must remain off of growth hormone for the duration of their participation.
Signed informed consent according to institutional guidelines must be obtained and patient must begin therapy within twenty eight (28) days.

Exclusion Criteria:

Patient must not be receiving any other experimental drug therapy.
Patients must not be taking medications that significantly affect the metabolism of lonafarnib.
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.