Trial Outcomes & Findings for Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) (NCT NCT01912274)

NCT ID: NCT01912274

Last Updated: 2021-02-09

Results Overview

Proportion of patients assessed as having achieved a disease response of either CR or CRi or MLFS according to the IWG criteria. CR (ie, complete remission defined as \<5% blasts in the bone marrow, no blasts with Auer rods, no extramedullary disease, ANC ≥1000/μL, and platelets ≥100,000/μL must be independent of transfusions for at least 1 week before each assessment). CRi (ie, morphologic complete remission with incomplete blood count recovery, defined as morphologic CR with residual neutropenia (\<1,000/μL) or residual thrombocytopenia (\<100,000/μL), no extramedullary disease, does not require transfusion independence) MLFS (ie, morphologic leukemia free state, defined as \<5% blasts in an aspirate sample with marrow spicules, no extramedullary disease, does not require transfusion independence)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

through study completion up to a maximum of three years

Results posted on

2021-02-09

Participant Flow

Participant milestones

Participant milestones
Measure	Pracinostat With Azacitadine 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Overall Study STARTED	50
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study of Pracinostat With Azacitadine in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pracinostat With Azacitadine n=50 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	50 Participants n=5 Participants
Age, Continuous	75 years n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Region of Enrollment United States	50 participants n=5 Participants

PRIMARY outcome

Timeframe: through study completion up to a maximum of three years

Population: ITT set

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=50 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Best Response Rate	26 Participants

SECONDARY outcome

Timeframe: through study completion up to a maximum of three years

proportion of patients with CR plus CRi plus MLFS plus PR plus PRi

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=50 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Overall Response Rate	32 Participants

SECONDARY outcome

Timeframe: through study completion up to a maximum of three years

Population: 17 patients had molecular abnormalities identified at baseline and were evaluable for assessing CRm.

proportion of patients assessed as having complete cytogenetic response (CRc) + molecular complete remission (CRm) to pracinostat plus azacitidine

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=17 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Complete Cytogenetic Response Plus Molecular Complete Remission	1 Participants

SECONDARY outcome

Timeframe: through study completion up to a maximum of three years

time from the first day of study administration to PD, relapse from CR/CRi/MLFS, lack of efficacy or death.

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=50 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Progression Free Survival	12.56 months Interval 10.03 to 17.7

SECONDARY outcome

Timeframe: through study completion up to a maximum of three years

time from the first day of study drug administration to death

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=50 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Overall Survival	19.08 months Interval 10.0 to 26.52

SECONDARY outcome

Timeframe: through study completion up to a maximum of 3 years

The duration of the best response to treatment with pracinostat plus azacitidine was determined by the Investigator for patients who achieved a CR, CRi, or MLFS. The duration was defined as the time from the initial determination of response to the time of relapse, PD, or death, whichever occurred first plus 1 day.

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=26 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Duration of Best Response	11.54 months Interval 8.3 to 17.18

SECONDARY outcome

Timeframe: through study completion up to a maximum of three years

The duration of the response to treatment with pracinostat plus azacitidine was determined by the Investigator for patients who achieved a CR, CRi, PR, PRi, or MLFS. The duration was defined as the time from the initial determination of response to the time of relapse, PD, or death, whichever occurred first plus 1 day.

Outcome measures

Outcome measures
Measure	Pracinostat With Azacitadine n=32 Participants 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Duration of Response	11.54 months Interval 8.3 to 17.18

Adverse Events

Pracinostat With Azacitadine

Serious events: 50 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pracinostat With Azacitadine n=50 participants at risk 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Infections and infestations pneumonia	6.0% 3/50 • through study completion up to a maximum of three years
Infections and infestations sepsis	6.0% 3/50 • through study completion up to a maximum of three years
Infections and infestations diverticulitis	4.0% 2/50 • through study completion up to a maximum of three years
Infections and infestations enterococcal bacteraemia	4.0% 2/50 • through study completion up to a maximum of three years
Infections and infestations oral infection	4.0% 2/50 • through study completion up to a maximum of three years
Infections and infestations pseudomonal bacteraemia	4.0% 2/50 • through study completion up to a maximum of three years
Infections and infestations septic shock	4.0% 2/50 • through study completion up to a maximum of three years
Infections and infestations urinarytract infection	4.0% 2/50 • through study completion up to a maximum of three years
Infections and infestations anal abscess	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations device relatedinfection	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Escherichia bacteraemia	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Escherichia urinary tract infection	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Lung infection	2.0% 1/50 • through study completion up to a maximum of three years
General disorders Neutropenic sepsis	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Parainfluenzae virus infection	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Periodontitis	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Pneumonia fungal	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations Sialoadenitis	2.0% 1/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders Pancytopenia	2.0% 1/50 • through study completion up to a maximum of three years
Cardiac disorders febrile neutropenia	32.0% 16/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders thrombocytopenia	2.0% 1/50 • through study completion up to a maximum of three years
Nervous system disorders Cerebrovascular accident	4.0% 2/50 • through study completion up to a maximum of three years
Nervous system disorders Syncope	4.0% 2/50 • through study completion up to a maximum of three years
Nervous system disorders Haemorrhage intracranial	2.0% 1/50 • through study completion up to a maximum of three years
Nervous system disorders headache	2.0% 1/50 • through study completion up to a maximum of three years
Infections and infestations cellulitis	8.0% 4/50 • through study completion up to a maximum of three years
Nervous system disorders Peripheral sensorimotor neuropathy	2.0% 1/50 • through study completion up to a maximum of three years
Nervous system disorders Presyncope	2.0% 1/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Gastrointestinal haemorrhage	4.0% 2/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Constipation	2.0% 1/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Inguinal hernia, obstructive	2.0% 1/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Melaena	2.0% 1/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Small intestinal obstruction	2.0% 1/50 • through study completion up to a maximum of three years
Cardiac disorders Atrial fibrillation	8.0% 4/50 • through study completion up to a maximum of three years
Cardiac disorders Cardiac tamponade	2.0% 1/50 • through study completion up to a maximum of three years
Metabolism and nutrition disorders Dehydration	4.0% 2/50 • through study completion up to a maximum of three years
Metabolism and nutrition disorders Failure to thrive	4.0% 2/50 • through study completion up to a maximum of three years
General disorders Fatigue	4.0% 2/50 • through study completion up to a maximum of three years
Skin and subcutaneous tissue disorders Pyrexia	2.0% 1/50 • through study completion up to a maximum of three years
General disorders Systemic inflammatory response syndrome	2.0% 1/50 • through study completion up to a maximum of three years
Musculoskeletal and connective tissue disorders Back pain	4.0% 2/50 • through study completion up to a maximum of three years
Musculoskeletal and connective tissue disorders Gouty arthritis	2.0% 1/50 • through study completion up to a maximum of three years
Respiratory, thoracic and mediastinal disorders Laryngeal ulceration	2.0% 1/50 • through study completion up to a maximum of three years
Respiratory, thoracic and mediastinal disorders pleural effusion	2.0% 1/50 • through study completion up to a maximum of three years
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	2.0% 1/50 • through study completion up to a maximum of three years
Investigations Electrocardiogram QT prolonged	2.0% 1/50 • through study completion up to a maximum of three years
Investigations Neutrophil count decreased	2.0% 1/50 • through study completion up to a maximum of three years
Vascular disorders Haematoma	2.0% 1/50 • through study completion up to a maximum of three years
Vascular disorders Hypotension	2.0% 1/50 • through study completion up to a maximum of three years
Injury, poisoning and procedural complications Allergic transfusion reaction	2.0% 1/50 • through study completion up to a maximum of three years
Renal and urinary disorders Renal failure acute	2.0% 1/50 • through study completion up to a maximum of three years

Other adverse events

Other adverse events
Measure	Pracinostat With Azacitadine n=50 participants at risk 60 mg of pracinostat by mouth 3 times a week for 3 weeks followed by 1 week of rest repeated every 28 days 75 mg/m2 azacitadine for the first 7 days of each 28 day cycle, via subcutaneous (SC) injection or intravenous (IV) infusion if SC injections are intolerable Pracinostat: Elderly newly diagnosed patients will all receive pracinostat Azacitidine: Elderly newly diagnosed patients will all receive azacitadine
Gastrointestinal disorders Nausea	48.0% 24/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Vomiting	26.0% 13/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Diarrhoea	22.0% 11/50 • through study completion up to a maximum of three years
Gastrointestinal disorders Constipation	14.0% 7/50 • through study completion up to a maximum of three years
General disorders Fatigue	40.0% 20/50 • through study completion up to a maximum of three years
General disorders Asthenia	14.0% 7/50 • through study completion up to a maximum of three years
General disorders Chills	10.0% 5/50 • through study completion up to a maximum of three years
Hepatobiliary disorders Pyrexia	10.0% 5/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders Thrombocytopenia	38.0% 19/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders Neutropenia	30.0% 15/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders Anaemia	22.0% 11/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders Febrile neutropenia	22.0% 11/50 • through study completion up to a maximum of three years
Blood and lymphatic system disorders Leukopenia	8.0% 4/50 • through study completion up to a maximum of three years
Investigations Weight decreased	12.0% 6/50 • through study completion up to a maximum of three years
Nervous system disorders Dizziness	8.0% 4/50 • through study completion up to a maximum of three years
Nervous system disorders Dysgeusia	6.0% 3/50 • through study completion up to a maximum of three years
Nervous system disorders Neuropathy peripheral	6.0% 3/50 • through study completion up to a maximum of three years
Metabolism and nutrition disorders Decreased appetite	22.0% 11/50 • through study completion up to a maximum of three years
Infections and infestations Pneumonia	6.0% 3/50 • through study completion up to a maximum of three years
Skin and subcutaneous tissue disorders Pruritus	6.0% 3/50 • through study completion up to a maximum of three years
Skin and subcutaneous tissue disorders Rash	6.0% 3/50 • through study completion up to a maximum of three years
Respiratory, thoracic and mediastinal disorders Cough	6.0% 3/50 • through study completion up to a maximum of three years
Musculoskeletal and connective tissue disorders Muscular weakness	6.0% 3/50 • through study completion up to a maximum of three years
Injury, poisoning and procedural complications Contusion	8.0% 4/50 • through study completion up to a maximum of three years

Additional Information

Edwin de Wit - Head of Clinical development

Helsinn HealthcareSA

Phone: + 41 919852121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place