A Safety and Efficacy Study of Pracinostat and Azacitidine in Patients With High Risk Myelodysplastic Syndromes
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|ClinicalTrials.gov Identifier: NCT03151304|
Recruitment Status : Unknown
Verified August 2018 by Helsinn Healthcare SA.
Recruitment status was: Active, not recruiting
First Posted : May 12, 2017
Last Update Posted : March 14, 2019
This is a Phase 2, two-stage study of the safety and efficacy of pracinostat in combination with azacitidine in patients with IPSS-R high and very high risk MDS who are previously untreated with HMAs. Enrollment in this study will be limited to high/very high risk MDS because this group represents the highest unmet need, with median survival of less than 18 months.
Stage 1a will be conducted as an open-label single arm in up to 40 subjects to assess if this regimen with a lower pracinostat dose results in a discontinuation rate that meets a predefined threshold and in efficacy that justifies expansion of enrollment into Stage 1b.
A discontinuation rate of approximately ≤10% in Stage 1a, a rate comparable to that observed with azacitidine alone in study MEI-003, supports expansion into Stage 1b.
Stage 1b will be conducted as expansion of stage 1a. Approximately 20 additional subjects will be enrolled. Study drugs should be continued until disease progression or intolerable toxicity. It is important to note that the median time to achieving a response with azacitidine alone is 4 to 5 months. Furthermore, the median time to achieving a CR in study MEI-003 was 4 cycles. Therefore, early (<6 months) discontinuation of trial therapy for 'no response' should be avoided. The Medical Monitor should be contacted prior to discontinuing a subject from the study to discuss the rationale for discontinuation.
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes||Drug: Pracinostat Drug: Azacitidine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Two-Stage, Open-Label|
|Masking:||None (Open Label)|
|Official Title:||A Two-Stage, Open-Label Phase 2 Study of Pracinostat and Azacitidine in Patients With IPSS-R High and Very High Risk Myelodysplastic Syndromes Previously Untreated With Hypomethylating Agents|
|Actual Study Start Date :||June 1, 2017|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||June 2020|
Experimental: Stage 1a and 1b open-label pracinostat plus azacitidine
open-label single arm pracinostat plus azacitidine. Pracinostat: 45 mg administered orally 3 days each week for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles.
In later cycles (i.e., after Cycle 4), pracinostat dose reduction to 45 mg orally 3 days each week × 2 weeks (instead of 3 weeks) or dose interruption is allowed to manage toxicity such as fatigue, gastrointestinal toxicity, or myelosuppression.
Azacitine: 75 mg/m2 for 7 days of each 28-day cycle. Administration will occur by subcutaneous (SC) injection, or IV infusion if SC injections are not tolerated, on one of two schedules:
45 mg capsule
Other Name: SB939
SC or IV injection
- overall response rate (ORR), [ Time Frame: 36 months ]Determine the rate of overall response rate (ORR), defined as complete remission (CR), partial remission (PR) and marrow CR, of pracinostat plus azacitidine in high/very high risk MDS
- Complete response (CR) rate [ Time Frame: 36 months ]the proportion of subjects with confirmed CR (i.e., 2 CRs at least 28 days apart) according to the IWG criteria
- Overall hematologic improvement (HI) response rate [ Time Frame: 36 months ]proportion of subjects who demonstrate major hematologic improvement as defined by the IWG criteria
- Clinical benefit rate [ Time Frame: 36 months ]defined as rate of CR + PR + HI + Marrow CR
- Rate of cytogenetic CR [ Time Frame: 36 months ]proportion of subjects with confirmed CR by cytogenetic assessment
- Duration of response (DoR) [ Time Frame: 36 months ]the time from the initial determination of response to the time of disease progression or death on study, whichever occurs first
- Rate of leukemic transformation [ Time Frame: 6, 12, 18 and 24 months ]transformation at landmark time points of 6 months, 12 months, 18 months, and 24 months
- event-free survival (EFS) [ Time Frame: 36 months ]time from the first day of study drug administration (Day 1) to failure or death from any cause
- progression-free survival (PFS) [ Time Frame: 36 months ]time from the first day of study drug administration (Day 1) to disease recurrence or progression as defined by the IWG criteria, or death on study
- overall survival (OS) [ Time Frame: form day 1 to death on study, assessed up to 36 months ]time from the first day of study drug administration (Day 1) to death on study
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03151304
|Study Director:||Richard Ghalie, MD||MEI Pharma|
|Study Chair:||Ehab Atallah, MD||Medical College of Wisconsin adn Froedtert Hospital|