Blood Disease, Bone Marrow Disease, Myelodysplastic Syndromes
Conditions
Brief summary
This study is to evaluate the efficacy, safety and tolerability of vorinostat in patients with lower risk Myelodysplastic Syndrome (MDS).
Interventions
DRUGvorinostat
vorinostat 400 mg by mouth (P.O.) capsules once daily (q.d.). Treatment in 21 day cycles for up to 8 cycles.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient is a male or female, at least 18 years of age with low or intermediate-1 risk Myelodysplastic Syndrome (MDS) defined by the International Prognostic Scoring System * Patient has previously untreated disease, or has received up to one prior treatment regimen for lower-risk Myelodysplastic Syndrome * Patient has a performance status of equal to or less than 2 on the Eastern Cooperative Oncology Group Performance Scale * Patient must have adequate organ function
Exclusion criteria
* Patient has clinical evidence of Central Nervous System (CNS) leukemia * Patient is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study * Patient had prior treatment with a histone deacetylase inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria | 2 Years | Number of responders is defined as the number of patients in the analysis population who have complete response (CR), partial response (PR), or hematologic improvement (HI) per International Working Group Response Criteria during the course of the study. Confirmation of CR or PR will require a second assessment performed 4 weeks or more after the initial assessment. Confirmation of HI will require a second assessment performed 8 weeks or more after the initial assessment. Number of non-responders is defined as the number of patients who did not achieve CR, PR or HI in the study. |
| Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | Every 21 days while on therapy and at 30 days after the last dose of study therapy | — |
Participant flow
Recruitment details
Date of first patient in was 26-Jun-2007. The date of last patient last visit for the study was 16-Jul-2009.
Pre-assignment details
Vorinostat was studied in patients who were first stratified by their International Prognostic Scoring System for myelodysplastic syndrome (low versus intermediate-1) and than randomized into one of two dose schedules.
Participants by arm
| Arm | Count |
|---|---|
| Vorinostat Once Daily Dose Schedule Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle. | 9 |
| Vorinostat Thrice Daily Dose Schedule Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle. | 12 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lack of Efficacy | 4 | 6 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Progressive Disease | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Vorinostat Once Daily Dose Schedule | Vorinostat Thrice Daily Dose Schedule | Total |
|---|---|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 18.5 | 64.0 years STANDARD_DEVIATION 10.5 | 66.0 years STANDARD_DEVIATION 14.1 |
| Eastern Cooperative Oncology Group (ECOG) Performance Scale Status 0 = Normal Activity | 4 participants | 10 participants | 14 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Scale Status 1 = Symptoms, but ambulatory | 4 participants | 1 participants | 5 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Scale Status 2 = In bed < 50% of the time | 1 participants | 1 participants | 2 participants |
| International Prognostic Scoring System Risk (IPSS) Intermediate-1 | 6 Participants | 8 Participants | 14 Participants |
| International Prognostic Scoring System Risk (IPSS) Low | 3 Participants | 4 Participants | 7 Participants |
| Prior Myelodysplastic Syndromes Therapy No | 3 Participants | 9 Participants | 12 Participants |
| Prior Myelodysplastic Syndromes Therapy Yes | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 9 participants | 10 participants | 19 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 9 | 12 / 12 |
| serious Total, serious adverse events | 2 / 9 | 5 / 12 |
Outcome results
Primary
Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria
Number of responders is defined as the number of patients in the analysis population who have complete response (CR), partial response (PR), or hematologic improvement (HI) per International Working Group Response Criteria during the course of the study. Confirmation of CR or PR will require a second assessment performed 4 weeks or more after the initial assessment. Confirmation of HI will require a second assessment performed 8 weeks or more after the initial assessment. Number of non-responders is defined as the number of patients who did not achieve CR, PR or HI in the study.
Time frame: 2 Years
Population: Full analysis set (FAS) population is the analysis population. This population consists of all randomized patients who have received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vorinostat Once Daily Dose Schedule | Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria | Responder | 0 Participants |
| Vorinostat Once Daily Dose Schedule | Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria | Non-responder | 9 Participants |
| Vorinostat Thrice Daily Dose Schedule | Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria | Responder | 0 Participants |
| Vorinostat Thrice Daily Dose Schedule | Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria | Non-responder | 12 Participants |
Primary
Safety and Tolerability as Assessed by the Number of Participants With Adverse Events.
Time frame: Every 21 days while on therapy and at 30 days after the last dose of study therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vorinostat Once Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With no adverse events | 0 Participants |
| Vorinostat Once Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With serious adverse events | 2 Participants |
| Vorinostat Once Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With drug-related adverse events | 4 Participants |
| Vorinostat Once Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With serious drug-related adverse events | 0 Participants |
| Vorinostat Once Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With one or more adverse events | 9 Participants |
| Vorinostat Thrice Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With serious drug-related adverse events | 2 Participants |
| Vorinostat Thrice Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With one or more adverse events | 12 Participants |
| Vorinostat Thrice Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With no adverse events | 0 Participants |
| Vorinostat Thrice Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With drug-related adverse events | 11 Participants |
| Vorinostat Thrice Daily Dose Schedule | Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. | With serious adverse events | 5 Participants |