This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Schering-Plough
Information provided by (Responsible Party):
Mark Kieran, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00879034
First received: April 8, 2009
Last updated: July 27, 2017
Last verified: July 2017
Results First Received: May 24, 2017  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: No masking;   Primary Purpose: Treatment
Conditions: Progeria
Hutchinson-Gilford Syndrome
Interventions: Drug: Lonafarnib
Drug: Zoledronic Acid
Drug: Pravastatin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
4 patients with classic HGPS from the United States were enrolled in March 2009 at Boston Children's Hospital. 1 additional patient had nonclassic mutations.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All patients screened to participate in study were consented onto the study as planned.

Reporting Groups
  Description
Zoledronic Acid, Pravastatin, and Lonafarnib Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.

Participant Flow:   Overall Study
    Zoledronic Acid, Pravastatin, and Lonafarnib
STARTED   5 
Received Treatment [1]   4 
COMPLETED   5 
NOT COMPLETED   0 
[1] One patient did not receive a zoledronic acid infusion during study.



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Zoledronic Acid, Pravastatin, and Lonafarnib Lonafarnib capsules are to be orally administered twice per day approximately every 12 hours. Lonafarnib dosing will begin at 150 mg/m2 by mouth twice daily. Dose levels are 150, 115, 90 and 70 mg/m2. Patients experiencing significant drug related grade 3 or 4 toxicity and not responding to therapy interruption or supportive care measures will be dose reduced by one dose level. Zoledronic acid will be administered intravenously at week one of this treatment trial. Week one administration will consist of one infusion over a 30 minute period, 0.0125 mg/kg body weight. Pravastatin will begin at 5 mg by mouth once daily for children weighing less than 10 kg, and 10 mg by mouth once daily for children weighing 10 kg or greater.

Baseline Measures
   Zoledronic Acid, Pravastatin, and Lonafarnib 
Overall Participants Analyzed 
[Units: Participants]
 5 
Age 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 5 
<=18 years      5 100.0% 
Between 18 and 65 years      0   0.0% 
>=65 years      0   0.0% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Participants Analyzed 
[Units: Participants]
 5 
Female      1  20.0% 
Male      4  80.0% 
Race and Ethnicity Not Collected [1] 
[Units: Participants]
Count of Participants
  
[1] Race and Ethnicity were not collected from any participant.
Region of Enrollment 
[Units: Participants]
 
United States   
Participants Analyzed 
[Units: Participants]
 5 
United States   5 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   The Primary Objective of This Study is to Evaluate the Feasibility of Administering Intravenous Zoledronic Acid, Oral Pravastatin and Oral Lonafarnib, to Patients With Progeria for a Minimum of 4 Weeks   [ Time Frame: 4 weeks ]

2.  Secondary:   To Describe Any Acute and Chronic Toxicities Associated With Treating Progeria Patients With the Combination of Zoledronic Acid, Pravastatin and Lonafarnib   [ Time Frame: 4 weeks ]

3.  Secondary:   To Investigate Which Clinical and Laboratory Studies Are Needed to Monitor or Alter Therapy to Prevent Unacceptable Toxicity   [ Time Frame: 4 weeks ]

4.  Secondary:   To Assess the Pharmacokinetics of Lonafarnib in Patients With Progeria.   [ Time Frame: 4 weeks ]

5.  Secondary:   To Assay for the Inhibition of HDJ-2 Farnesylation in Peripheral Blood Leukocytes (PBL)   [ Time Frame: 4 weeks ]

6.  Secondary:   To Obtain Baseline Clinical and Laboratory Data so That Longer-term Measures of Efficacy Will be Achievable if Treatment Continues Beyond the 4-week Feasibility Study Period.   [ Time Frame: 4 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This was an open label clinical trial on a very rare disease population. Patient numbers are small, though 5 participants represents a small but significant portion of the world's population of children with HGPS.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Dr. Mark Kieran
Organization: Dana-Farber Cancer Institute
phone: 617-632-4907
e-mail: mark_kieran@dfci.harvard.edu


Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Mark Kieran, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00879034     History of Changes
Other Study ID Numbers: 09-02-0074
P06087 ( Other Identifier: Schering-Plough )
Study First Received: April 8, 2009
Results First Received: May 24, 2017
Last Updated: July 27, 2017