UPDATED RESULTS FROM A PHASE 2 STUDY OF PRACINOSTAT (P) IN COMBINATION WITH AZACITIDINE (AZA) IN ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA (AML)
(Abstract release date: 05/21/15)
EHA Library. Garcia-Manero G. 06/13/15; 100709; P568
Guillermo Garcia-Manero
Contributions
Contributions
Abstract
Abstract: P568
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options. We previously reported a high initial response rate in the first stage of a phase 2 study of P plus AZA in this population (ASH 2014). This report presents updated results, which include additional patients.
Aims
The study was designed to evaluate the efficacy and safety of the combination of pracinostat and azacitidine in elderly patients with AML
Methods
Eligibility includes previously untreated AML (≥ 20% bone marrow blasts), age ≥ 65 years, unsuitable for intensive therapy due to co-morbidities and/or AML related features, and intermediate or high-risk cytogenetics. Study therapy includes P, 60 mg p.o. 3 alternate days/week for 3 weeks plus AZA, 75 mg/m2 /day 1-7 or day 1-5 and 8-9 either s.c. or i.v. with cycles repeated every 28 days until progressive disease, lack of response, or intolerance. The primary endpoint is CR+CRi+ morphologic leukemia free state (MLFS) per IWG criteria. Response assessments occur at the end of cycle 1 or 2 then every other cycle or when clinically indicated. A Simon 2-stage statistical design is utilized with the following assumptions: null=0.10, alternate=0.25, α=0.10, power=0.90. Stage 1 n=27 and total stage 2 n=40.
Results
Between 12/2013 and 12/2014 50 patients from 15 study sites were enrolled. At this time, 47 are evaluable for efficacy. Baseline disease characteristics for all patients include: median age 75 (range 66-84); 32 de novo AML, 13 evolved from AHD, 5 treatment-related; 28 intermediate-risk and 20 high-risk cytogenetics and 2 unknown; baseline bone marrow blast counts ranged from 20% to 89% with a median of 40%. The primary endpoint of CR +CRi +MLFS has been observed in 22/47 evaluable patients (47%) to date, including 14/47 (30%) CR. Current median duration of response is 15+ weeks (range: 1– 48+ weeks). Disease progression has not been observed in any responders. 30 patients continue on study (range 11- 52+ weeks). The 60-day all-cause mortality rate is 10% (5/50). Median overall survival has not been reached. Treatment emergent adverse events (TEAEs) Grade ≥ 3 seen in >5% of patients: febrile neutropenia 30%; thrombocytopenia 22%; neutropenia 10%; cellulitis 10%; anemia 8%; fatigue 8%; sepsis 6%, and pancytopenia 6%. TEAE’s leading to study therapy discontinuation: peripheral motor neuropathy (1), parainfluenza (1), atrial fibrillation/prolonged QTc/(1), subdural hematoma after a fall (1), and sepsis (3).
Summary
P plus AZA produces a high rate of durable responses in this AML population. Updated data, including EFS and OS estimates, will be presented at the meeting. These phase 2 data warrant definitive evaluation in a phase 3 study.
Keyword(s): Acute leukemia, Elderly
Session topic: Acute myeloid leukemia - Clinical 3
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options. We previously reported a high initial response rate in the first stage of a phase 2 study of P plus AZA in this population (ASH 2014). This report presents updated results, which include additional patients.
Aims
The study was designed to evaluate the efficacy and safety of the combination of pracinostat and azacitidine in elderly patients with AML
Methods
Eligibility includes previously untreated AML (≥ 20% bone marrow blasts), age ≥ 65 years, unsuitable for intensive therapy due to co-morbidities and/or AML related features, and intermediate or high-risk cytogenetics. Study therapy includes P, 60 mg p.o. 3 alternate days/week for 3 weeks plus AZA, 75 mg/m2 /day 1-7 or day 1-5 and 8-9 either s.c. or i.v. with cycles repeated every 28 days until progressive disease, lack of response, or intolerance. The primary endpoint is CR+CRi+ morphologic leukemia free state (MLFS) per IWG criteria. Response assessments occur at the end of cycle 1 or 2 then every other cycle or when clinically indicated. A Simon 2-stage statistical design is utilized with the following assumptions: null=0.10, alternate=0.25, α=0.10, power=0.90. Stage 1 n=27 and total stage 2 n=40.
Results
Between 12/2013 and 12/2014 50 patients from 15 study sites were enrolled. At this time, 47 are evaluable for efficacy. Baseline disease characteristics for all patients include: median age 75 (range 66-84); 32 de novo AML, 13 evolved from AHD, 5 treatment-related; 28 intermediate-risk and 20 high-risk cytogenetics and 2 unknown; baseline bone marrow blast counts ranged from 20% to 89% with a median of 40%. The primary endpoint of CR +CRi +MLFS has been observed in 22/47 evaluable patients (47%) to date, including 14/47 (30%) CR. Current median duration of response is 15+ weeks (range: 1– 48+ weeks). Disease progression has not been observed in any responders. 30 patients continue on study (range 11- 52+ weeks). The 60-day all-cause mortality rate is 10% (5/50). Median overall survival has not been reached. Treatment emergent adverse events (TEAEs) Grade ≥ 3 seen in >5% of patients: febrile neutropenia 30%; thrombocytopenia 22%; neutropenia 10%; cellulitis 10%; anemia 8%; fatigue 8%; sepsis 6%, and pancytopenia 6%. TEAE’s leading to study therapy discontinuation: peripheral motor neuropathy (1), parainfluenza (1), atrial fibrillation/prolonged QTc/(1), subdural hematoma after a fall (1), and sepsis (3).
Summary
P plus AZA produces a high rate of durable responses in this AML population. Updated data, including EFS and OS estimates, will be presented at the meeting. These phase 2 data warrant definitive evaluation in a phase 3 study.
Keyword(s): Acute leukemia, Elderly
Session topic: Acute myeloid leukemia - Clinical 3
Abstract: P568
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options. We previously reported a high initial response rate in the first stage of a phase 2 study of P plus AZA in this population (ASH 2014). This report presents updated results, which include additional patients.
Aims
The study was designed to evaluate the efficacy and safety of the combination of pracinostat and azacitidine in elderly patients with AML
Methods
Eligibility includes previously untreated AML (≥ 20% bone marrow blasts), age ≥ 65 years, unsuitable for intensive therapy due to co-morbidities and/or AML related features, and intermediate or high-risk cytogenetics. Study therapy includes P, 60 mg p.o. 3 alternate days/week for 3 weeks plus AZA, 75 mg/m2 /day 1-7 or day 1-5 and 8-9 either s.c. or i.v. with cycles repeated every 28 days until progressive disease, lack of response, or intolerance. The primary endpoint is CR+CRi+ morphologic leukemia free state (MLFS) per IWG criteria. Response assessments occur at the end of cycle 1 or 2 then every other cycle or when clinically indicated. A Simon 2-stage statistical design is utilized with the following assumptions: null=0.10, alternate=0.25, α=0.10, power=0.90. Stage 1 n=27 and total stage 2 n=40.
Results
Between 12/2013 and 12/2014 50 patients from 15 study sites were enrolled. At this time, 47 are evaluable for efficacy. Baseline disease characteristics for all patients include: median age 75 (range 66-84); 32 de novo AML, 13 evolved from AHD, 5 treatment-related; 28 intermediate-risk and 20 high-risk cytogenetics and 2 unknown; baseline bone marrow blast counts ranged from 20% to 89% with a median of 40%. The primary endpoint of CR +CRi +MLFS has been observed in 22/47 evaluable patients (47%) to date, including 14/47 (30%) CR. Current median duration of response is 15+ weeks (range: 1– 48+ weeks). Disease progression has not been observed in any responders. 30 patients continue on study (range 11- 52+ weeks). The 60-day all-cause mortality rate is 10% (5/50). Median overall survival has not been reached. Treatment emergent adverse events (TEAEs) Grade ≥ 3 seen in >5% of patients: febrile neutropenia 30%; thrombocytopenia 22%; neutropenia 10%; cellulitis 10%; anemia 8%; fatigue 8%; sepsis 6%, and pancytopenia 6%. TEAE’s leading to study therapy discontinuation: peripheral motor neuropathy (1), parainfluenza (1), atrial fibrillation/prolonged QTc/(1), subdural hematoma after a fall (1), and sepsis (3).
Summary
P plus AZA produces a high rate of durable responses in this AML population. Updated data, including EFS and OS estimates, will be presented at the meeting. These phase 2 data warrant definitive evaluation in a phase 3 study.
Keyword(s): Acute leukemia, Elderly
Session topic: Acute myeloid leukemia - Clinical 3
Type: Poster Presentation
Presentation during EHA20: From 13.06.2015 17:15 to 13.06.2015 18:45
Location: Poster area (Hall C)
Background
Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options. We previously reported a high initial response rate in the first stage of a phase 2 study of P plus AZA in this population (ASH 2014). This report presents updated results, which include additional patients.
Aims
The study was designed to evaluate the efficacy and safety of the combination of pracinostat and azacitidine in elderly patients with AML
Methods
Eligibility includes previously untreated AML (≥ 20% bone marrow blasts), age ≥ 65 years, unsuitable for intensive therapy due to co-morbidities and/or AML related features, and intermediate or high-risk cytogenetics. Study therapy includes P, 60 mg p.o. 3 alternate days/week for 3 weeks plus AZA, 75 mg/m2 /day 1-7 or day 1-5 and 8-9 either s.c. or i.v. with cycles repeated every 28 days until progressive disease, lack of response, or intolerance. The primary endpoint is CR+CRi+ morphologic leukemia free state (MLFS) per IWG criteria. Response assessments occur at the end of cycle 1 or 2 then every other cycle or when clinically indicated. A Simon 2-stage statistical design is utilized with the following assumptions: null=0.10, alternate=0.25, α=0.10, power=0.90. Stage 1 n=27 and total stage 2 n=40.
Results
Between 12/2013 and 12/2014 50 patients from 15 study sites were enrolled. At this time, 47 are evaluable for efficacy. Baseline disease characteristics for all patients include: median age 75 (range 66-84); 32 de novo AML, 13 evolved from AHD, 5 treatment-related; 28 intermediate-risk and 20 high-risk cytogenetics and 2 unknown; baseline bone marrow blast counts ranged from 20% to 89% with a median of 40%. The primary endpoint of CR +CRi +MLFS has been observed in 22/47 evaluable patients (47%) to date, including 14/47 (30%) CR. Current median duration of response is 15+ weeks (range: 1– 48+ weeks). Disease progression has not been observed in any responders. 30 patients continue on study (range 11- 52+ weeks). The 60-day all-cause mortality rate is 10% (5/50). Median overall survival has not been reached. Treatment emergent adverse events (TEAEs) Grade ≥ 3 seen in >5% of patients: febrile neutropenia 30%; thrombocytopenia 22%; neutropenia 10%; cellulitis 10%; anemia 8%; fatigue 8%; sepsis 6%, and pancytopenia 6%. TEAE’s leading to study therapy discontinuation: peripheral motor neuropathy (1), parainfluenza (1), atrial fibrillation/prolonged QTc/(1), subdural hematoma after a fall (1), and sepsis (3).
Summary
P plus AZA produces a high rate of durable responses in this AML population. Updated data, including EFS and OS estimates, will be presented at the meeting. These phase 2 data warrant definitive evaluation in a phase 3 study.
Keyword(s): Acute leukemia, Elderly
Session topic: Acute myeloid leukemia - Clinical 3
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