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Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT01000155
Recruitment Status : Terminated (The study terminated early due to slow accrual.)
First Posted : October 22, 2009
Results First Posted : October 8, 2015
Last Update Posted : July 21, 2017
Sponsor:
Collaborators:
Brigham and Women's Hospital
Boston Children’s Hospital
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Maureen Okam, MD, MPH, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Sickle Cell Disease
Sickle Cell Anemia
Intervention Drug: vorinostat
Enrollment 5
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vorinostat
Hide Arm/Group Description Patients received vorinostat in a pulsed fashion, once a day for 3 consecutive days every week to a maximum dose of 400 mg per dose (1200 mg/wk), for 12 to 16 weeks at the maximum dose. The first 3 patients were enrolled in an intrapatient dose escalation schedule of 100 mg/d, then 200 mg/d, each for 3 consecutive days a week for 4 weeks, and then 400 mg/d, 3 consecutive days per week for 16 weeks. The last 2 patients were enrolled to receive 400 mg/d, 3 consecutive days per week for 12 weeks, without an initial dose escalation.
Period Title: Overall Study
Started 5
Completed 3
Not Completed 2
Reason Not Completed
Withdrawal by Subject             1
Adverse Event             1
Arm/Group Title Vorinostat
Hide Arm/Group Description Patients received vorinostat in a pulsed fashion, once a day for 3 consecutive days every week to a maximum dose of 400 mg per dose (1200 mg/wk), for 12 to 16 weeks at the maximum dose. The first 3 patients were enrolled in an intrapatient dose escalation schedule of 100 mg/d, then 200 mg/d, each for 3 consecutive days a week for 4 weeks, and then 400 mg/d, 3 consecutive days per week for 16 weeks. The last 2 patients were enrolled to receive 400 mg/d, 3 consecutive days per week for 12 weeks, without an initial dose escalation.
Overall Number of Baseline Participants 5
Hide Baseline Analysis Population Description
The analysis dataset is comprised of all treated patients.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants
37
(21 to 44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants
Female
3
  60.0%
Male
2
  40.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 5 participants
5
 100.0%
1.Primary Outcome
Title Percent Fetal Hemoglobin (HbF%) Induction Success Rate
Hide Description Success will be defined by comparing the maximum HbF% on study drug to the HbF% at baseline. An absolute increase in HbF% of 4% of more, or an increase to 100% or more of baseline in patients with HbF under 4% at baseline will be considered a success. HbF% induction success rate is calculated as the count of successes divided by the count of patients in the analysis population.
Time Frame HbF% was measured at baseline and weekly on treatment. Median duration of treatment was 3 months.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Vorinostat
Hide Arm/Group Description:
Patients received vorinostat in a pulsed fashion, once a day for 3 consecutive days every week to a maximum dose of 400 mg per dose (1200 mg/wk), for 12 to 16 weeks at the maximum dose. The first 3 patients were enrolled in an intrapatient dose escalation schedule of 100 mg/d, then 200 mg/d, each for 3 consecutive days a week for 4 weeks, and then 400 mg/d, 3 consecutive days per week for 16 weeks. The last 2 patients were enrolled to receive 400 mg/d, 3 consecutive days per week for 12 weeks, without an initial dose escalation.
Overall Number of Participants Analyzed 5
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: proportion of patients
0.20
(.01 to .65)
2.Secondary Outcome
Title F-Cell Percentage Level
Hide Description F-cell percentage levels were estimated based on established methods.
Time Frame Measured at baseline and end of treatment, up to 16 weeks.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Vorinostat
Hide Arm/Group Description:
Patients received vorinostat in a pulsed fashion, once a day for 3 consecutive days every week to a maximum dose of 400 mg per dose (1200 mg/wk), for 12 to 16 weeks at the maximum dose. The first 3 patients were enrolled in an intrapatient dose escalation schedule of 100 mg/d, then 200 mg/d, each for 3 consecutive days a week for 4 weeks, and then 400 mg/d, 3 consecutive days per week for 16 weeks. The last 2 patients were enrolled to receive 400 mg/d, 3 consecutive days per week for 12 weeks, without an initial dose escalation.
Overall Number of Participants Analyzed 5
Median (Full Range)
Unit of Measure: F-cell percentage
Baseline
9.8 [1] 
(NA to NA)
End of Treatment
12.1 [1] 
(NA to NA)
[1]
This information was not provided at the time of the analysis and the data are no longer accessible.
3.Secondary Outcome
Title γ-globin to β-globin Ratio
Hide Description Levels of peripheral blood γ-globin to β-globin messenger RNA were estimated based on established methods. The ratio of γ-globin to β-globin was then calculated.
Time Frame Measured at baseline and end of treatment, up to 16 weeks.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The analysis dataset is comprised of all treated patients.
Arm/Group Title Vorinostat
Hide Arm/Group Description:
Patients received vorinostat in a pulsed fashion, once a day for 3 consecutive days every week to a maximum dose of 400 mg per dose (1200 mg/wk), for 12 to 16 weeks at the maximum dose. The first 3 patients were enrolled in an intrapatient dose escalation schedule of 100 mg/d, then 200 mg/d, each for 3 consecutive days a week for 4 weeks, and then 400 mg/d, 3 consecutive days per week for 16 weeks. The last 2 patients were enrolled to receive 400 mg/d, 3 consecutive days per week for 12 weeks, without an initial dose escalation.
Overall Number of Participants Analyzed 5
Median (Full Range)
Unit of Measure: Change in γ-globin to β-globin ratio
0.89
(0.34 to 1.4)
Time Frame Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
Adverse Event Reporting Description Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3. Maximum grade toxicity by type was calculated within each group.
 
Arm/Group Title Vorinostat
Hide Arm/Group Description Patients received vorinostat in a pulsed fashion, once a day for 3 consecutive days every week to a maximum dose of 400 mg per dose (1200 mg/wk), for 12 to 16 weeks at the maximum dose. The first 3 patients were enrolled in an intrapatient dose escalation schedule of 100 mg/d, then 200 mg/d, each for 3 consecutive days a week for 4 weeks, and then 400 mg/d, 3 consecutive days per week for 16 weeks. The last 2 patients were enrolled to receive 400 mg/d, 3 consecutive days per week for 12 weeks, without an initial dose escalation.
All-Cause Mortality
Vorinostat
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vorinostat
Affected / at Risk (%)
Total   1/5 (20.00%) 
General disorders   
Constitutional, other  1  1/5 (20.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Vorinostat
Affected / at Risk (%)
Total   4/5 (80.00%) 
Gastrointestinal disorders   
Necrosis, pancreas  1  1/5 (20.00%) 
Ascites (non-malignant)  1  1/5 (20.00%) 
Stenosis (incl anastomotic) duodenum  1  1/5 (20.00%) 
Investigations   
Bilirubin  1  1/5 (20.00%) 
Metabolism and nutrition disorders   
Alkalosis  1  1/5 (20.00%) 
Renal and urinary disorders   
IV116  1  1/5 (20.00%) 
Skin and subcutaneous tissue disorders   
Sweating  1  1/5 (20.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
The trial did not meet it's accrual goal due to slow accrual.
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: Maureen Okam, MD, MPH
Organization: Brigham&Women's Hospital
Phone: 617-732-5048
Responsible Party: Maureen Okam, MD, MPH, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01000155     History of Changes
Other Study ID Numbers: 09-237
First Submitted: October 20, 2009
First Posted: October 22, 2009
Results First Submitted: September 9, 2015
Results First Posted: October 8, 2015
Last Update Posted: July 21, 2017