Conditions: Myelodysplastic Syndrome
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 21
Healthy volunteers: no

Brief summary:
Azacytidine (AZA) is the current standard of care for frontline patient treated with high-risk MDS and is clinically active in all type of MDS, however, 50% of the patients will never respond. Vorinostat is an orally available HDAC inhibitor with clinical activity in MDS and proven in vitro synergy with AZA. Patient treated upfront with a combination of this agents have shown more responses based on phase I/II data. In the present study, we will use the combination of these two drugs to try to create a synergetic effect and generate a response for patients who experienced treatment failure after AZA.

All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days. Study Design

Detailed description:
Patients who meet eligibility criteria will be administered vorinostat orally at 300mg two times daily for 7 days as outlined in table 1.1. AZA will be administered SC at 75 mg/m2/day x 7 consecutive days or at maximum tolerated dose if a dose reduction of AZA was needed before entering the trial with a minimum dose of 50mg/m2/d for 7 consecutive days.

Each cycle will last 28 days with AZA starting on day 1 of each cycle and vorinostat starting on day 3.

Patients will receive 6 cycles unless progression is documented. Patients with a complete remission (CR), partial remission (PR), or hematological improvement (HI), will be treated until progression.

Arms:
arm 1: Patients who meet eligibility criteria will be administered vorinostat orally at 300mg two times daily for 7 days. AZA will be administered SC at 75 mg/m2/day x 7 consecutive days or at maximum tolerated dose if a dose reduction of AZA was needed before entering the trial with a minimum dose of 50mg/m2/d for 7 consecutive days.

Each cycle will last 28 days with AZA starting on day 1 of each cycle and vorinostat starting on day 3.

Interventions: intervention 1: Azacitidine and oral vorinostat
Intervention descriptions: intervention 1: In patients still responding after six cycles, the drugs will continue to be supplied, and follow up until death or unacceptable tolerance will be continued in all patients.

Protocol document: