Trial Outcomes & Findings for Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease (NCT NCT01000155)
NCT ID: NCT01000155
Last Updated: 2017-07-21
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
5 participants
Primary outcome timeframe
HbF% was measured at baseline and weekly on treatment. Median duration of treatment was 3 months.
Results posted on
2017-07-21
Participant Flow
Participant milestones
| Measure |
Vorinostat
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 Study
STARTED
|
5
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Vorinostat
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 Study
Withdrawal by Subject
|
1
|
|
Overall Study
Adverse Event
|
1
|
Baseline Characteristics
Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
Vorinostat
n=5 Participants
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.
|
|---|---|
|
Age, Continuous
|
37 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: HbF% was measured at baseline and weekly on treatment. Median duration of treatment was 3 months.Population: The analysis dataset is comprised of all treated patients.
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.
Outcome measures
| Measure |
Vorinostat
n=5 Participants
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.
|
|---|---|
|
Percent Fetal Hemoglobin (HbF%) Induction Success Rate
|
0.20 proportion of patients
Interval 0.01 to 0.65
|
SECONDARY outcome
Timeframe: Measured at baseline and end of treatment, up to 16 weeks.Population: The analysis dataset is comprised of all treated patients.
F-cell percentage levels were estimated based on established methods.
Outcome measures
| Measure |
Vorinostat
n=5 Participants
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.
|
|---|---|
|
F-Cell Percentage Level
Baseline
|
9.8 F-cell percentage
This information was not provided at the time of the analysis and the data are no longer accessible.
|
|
F-Cell Percentage Level
End of Treatment
|
12.1 F-cell percentage
This information was not provided at the time of the analysis and the data are no longer accessible.
|
SECONDARY outcome
Timeframe: Measured at baseline and end of treatment, up to 16 weeks.Population: The analysis dataset is comprised of all treated patients.
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.
Outcome measures
| Measure |
Vorinostat
n=5 Participants
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.
|
|---|---|
|
γ-globin to β-globin Ratio
|
0.89 Change in γ-globin to β-globin ratio
Interval 0.34 to 1.4
|
Adverse Events
Vorinostat
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorinostat
n=5 participants at risk
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.
|
|---|---|
|
General disorders
Constitutional, other
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
Other adverse events
| Measure |
Vorinostat
n=5 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Necrosis, pancreas
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
|
Renal and urinary disorders
IV116
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
|
Gastrointestinal disorders
Ascites (non-malignant)
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
|
Gastrointestinal disorders
Stenosis (incl anastomotic) duodenum
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
|
Investigations
Bilirubin
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
|
Metabolism and nutrition disorders
Alkalosis
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
|
Skin and subcutaneous tissue disorders
Sweating
|
20.0%
1/5 • Assessed weekly throughout treatment from time of first dose and up to day 30 post-treatment. Median duration of treatment was 3 months.
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place