Trial Outcomes & Findings for Addition of Vorinostat to Azacitidine in Higher Risk MDS a Phase II add-on Study in Patients With Azacitidine Failure (NCT NCT01748240)

Results Overview

All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days. The response rate (CR, PR, HI or marrow CR) will be evaluated after six cycles, according to IWG 2006. 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. Complete Response (CR): Bone marrow: less than 5% myeloblasts with Peripheral blood: HI responses). Partial remission (RP): Bone marrow blasts decreased by at least 50% but still more than 5% with Peripheral blood: HI responses). Marrow CR:Bone marrow: maximum of 5% myeloblasts and decrease by at least 50% over pretreatment HI (hematologic improvement) * Erythroid response: Hgb increase at least by 1.5 g/dL * Platelet response: Increase from less than 20x109/L to more than 20x109/L and by at least 100% * Neutrophil response: At least 100% increase and an absolute increase of at least 0.5x109/L

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

6 month

Results posted on

2019-06-04

Participant Flow

Participant milestones

Participant milestones
Measure	Azacitidine and Oral Vorinostat 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. Azacitidine and oral vorinostat: 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.
Overall Study STARTED	21
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Addition of Vorinostat to Azacitidine in Higher Risk MDS a Phase II add-on Study in Patients With Azacitidine Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Azacitidine and Oral Vorinostat n=21 Participants 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. Azacitidine and oral vorinostat: 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants
Age, Continuous	72 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Region of Enrollment France	21 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 month

All eligible patients will be treated with Azacitidine and oral vorinostat for 6 cycles of 28 days. The response rate (CR, PR, HI or marrow CR) will be evaluated after six cycles, according to IWG 2006. 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. Complete Response (CR): Bone marrow: less than 5% myeloblasts with Peripheral blood: HI responses). Partial remission (RP): Bone marrow blasts decreased by at least 50% but still more than 5% with Peripheral blood: HI responses). Marrow CR:Bone marrow: maximum of 5% myeloblasts and decrease by at least 50% over pretreatment HI (hematologic improvement) * Erythroid response: Hgb increase at least by 1.5 g/dL * Platelet response: Increase from less than 20x109/L to more than 20x109/L and by at least 100% * Neutrophil response: At least 100% increase and an absolute increase of at least 0.5x109/L

Outcome measures

Outcome measures
Measure	Azacitidine and Oral Vorinostat n=21 Participants 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. Azacitidine and oral vorinostat: 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.
Response Rate	5 percentage of response Interval 0.0 to 24.0

Adverse Events

Azacitidine and Oral Vorinostat

Serious events: 14 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Azacitidine and Oral Vorinostat n=21 participants at risk 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. Azacitidine and oral vorinostat: 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.
Blood and lymphatic system disorders febrile neutropenia	66.7% 14/21 • Number of events 14

Other adverse events

Other adverse events
Measure	Azacitidine and Oral Vorinostat n=21 participants at risk 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. Azacitidine and oral vorinostat: 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.
Gastrointestinal disorders diarrhea	9.5% 2/21 • Number of events 2
Gastrointestinal disorders nausea	14.3% 3/21 • Number of events 3
Gastrointestinal disorders vomiting	9.5% 2/21 • Number of events 2
Gastrointestinal disorders constipation	9.5% 2/21 • Number of events 2
Gastrointestinal disorders undernutrition	4.8% 1/21 • Number of events 1

Additional Information

Groupe Francophone des Myelodysplasies

academic group

Phone: + 33 (0)1 71 20 70 59

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60