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An Efficacy and Safety Study Of Pracinostat In Combination With Azacitidine In Adults With Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03151408
Recruitment Status : Terminated (The IDMC recommended to stop the study prematurely due to a lack of efficacy.)
First Posted : May 12, 2017
Results First Posted : March 10, 2022
Last Update Posted : March 10, 2022
Sponsor:
Collaborator:
Clinipace Worldwide
Information provided by (Responsible Party):
Helsinn Healthcare SA

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia
Interventions Drug: Pracinostat
Drug: Placebos
Drug: Azacitidine
Enrollment 406
Recruitment Details

Approx. 130 sites worldwide (planned), 116 sites where patients were randomized. Date of 1st patient screened: 12 Jul 2017 and Date of last patient completed: 08 Aug 2020

A total of 725 patients were screened. Of these, 319 were considered screening failures, so a total of 406 patients were randomized

Pre-assignment Details Based on request of the IDMC, the interim analysis was actually done on 30Jun2020 when 232/390 events occurred in the study, The study was stopped for futility.
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Period Title: Overall Study
Started 203 [1] 203 [1]
Treated 201 201
Completed 0 0
Not Completed 203 203
Reason Not Completed
Adverse Event             24             23
Death             46             26
Physician Decision             13             19
Withdrawal by Subject             16             20
Progressive disease             45             61
non-compliance by patient             1             0
other reasons             56             52
randomized and not treated             2             2
[1]
Screened patients
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA Total
Hide Arm/Group Description

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Total of all reporting groups
Overall Number of Baseline Participants 203 203 406
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
7
   3.4%
5
   2.5%
12
   3.0%
>=65 years
196
  96.6%
198
  97.5%
394
  97.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 203 participants 203 participants 406 participants
75.4  (5.48) 75.1  (5.91) 75.3  (5.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Female
87
  42.9%
87
  42.9%
174
  42.9%
Male
116
  57.1%
116
  57.1%
232
  57.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
American Indian or Alaska Native
0
   0.0%
1
   0.5%
1
   0.2%
Asian
27
  13.3%
26
  12.8%
53
  13.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.5%
1
   0.2%
Black or African American
2
   1.0%
4
   2.0%
6
   1.5%
White
149
  73.4%
140
  69.0%
289
  71.2%
More than one race
3
   1.5%
3
   1.5%
6
   1.5%
Unknown or Not Reported
22
  10.8%
28
  13.8%
50
  12.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Australia
34
  16.7%
29
  14.3%
63
  15.5%
Argentina
3
   1.5%
2
   1.0%
5
   1.2%
Brazil
10
   4.9%
15
   7.4%
25
   6.2%
Czechia
10
   4.9%
8
   3.9%
18
   4.4%
France
8
   3.9%
10
   4.9%
18
   4.4%
Germany
5
   2.5%
6
   3.0%
11
   2.7%
Hungary
12
   5.9%
14
   6.9%
26
   6.4%
Italy
19
   9.4%
11
   5.4%
30
   7.4%
Poland
21
  10.3%
13
   6.4%
34
   8.4%
South Korea
8
   3.9%
7
   3.4%
15
   3.7%
Romania
10
   4.9%
7
   3.4%
17
   4.2%
Spain
24
  11.8%
28
  13.8%
52
  12.8%
Taiwan
17
   8.4%
18
   8.9%
35
   8.6%
United Kingdom
6
   3.0%
11
   5.4%
17
   4.2%
United States
12
   5.9%
18
   8.9%
30
   7.4%
Austria
4
   2.0%
6
   3.0%
10
   2.5%
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 203 participants 203 participants 406 participants
165.1  (10.23) 165.7  (8.96) 165.4  (9.61)
Smoking Habits  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Non-smoker
130
  64.0%
121
  59.6%
251
  61.8%
Ex-smoker
73
  36.0%
79
  38.9%
152
  37.4%
Current smoker
0
   0.0%
3
   1.5%
3
   0.7%
Cytogenetic Risk Category (central Lab results)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Intermediate
109
  53.7%
107
  52.7%
216
  53.2%
Unfavorable
51
  25.1%
60
  29.6%
111
  27.3%
Missing
43
  21.2%
36
  17.7%
79
  19.5%
[1]
Measure Description:

Favorable: inv(16)/t(16;16)/del(16q), t(15;17) with/without secondary aberrations; t(8;21) lacking del (9q) or lacking complex karyotypes.

Intermediate: Normal, +8, +6, -Y, del(12p)

Unfavorable: del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities)

Unknown: All other abnormalities

Cytogenetic Risk Category (local or central Lab results used for randomization)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Intermediate
136
  67.0%
135
  66.5%
271
  66.7%
unfavorable
67
  33.0%
68
  33.5%
135
  33.3%
[1]
Measure Description:

Favorable: inv(16)/t(16;16)/del(16q), t(15;17) with/without secondary aberrations; t(8;21) lacking del (9q) or lacking complex karyotypes.

Intermediate: Normal, +8, +6, -Y, del(12p)

Unfavorable: del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22) and complex karyotypes (≥ 3 unrelated abnormalities)

Unknown: All other abnormalities

ECOG PS (used for randomization)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Grade 0-1
113
  55.7%
114
  56.2%
227
  55.9%
Grade 2
90
  44.3%
89
  43.8%
179
  44.1%
[1]
Measure Description:

Grade and Descriptions

0 - Fully active, able to carry on all pre-disease performance without restriction.

  1. - Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).
  2. - Ambulatory and capable of all selfcare, but unable to carry out any work activities; and about more than 50% of waking hours.
  3. - Capable of only limited self-care; confined to bed or chair more than 50% of waking hours.
  4. - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
  5. - Dead
ECOG PS (at cycle 1 Day 1)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Grade 0-1
114
  56.2%
110
  54.2%
224
  55.2%
Grade 2
85
  41.9%
88
  43.3%
173
  42.6%
Grade 3
0
   0.0%
1
   0.5%
1
   0.2%
Missing
4
   2.0%
4
   2.0%
8
   2.0%
[1]
Measure Description:

Grade and Descriptions

0 - Fully active, able to carry on all pre-disease performance without restriction.

  1. - Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work).
  2. - Ambulatory and capable of all selfcare, but unable to carry out any work activities; and about more than 50% of waking hours.
  3. - Capable of only limited self-care; confined to bed or chair more than 50% of waking hours.
  4. - Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
  5. - Dead
Renal impairment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 203 participants 203 participants 406 participants
Normal or high: ≥ 90 mL/mg/1.73 m2
24
  11.8%
28
  13.8%
52
  12.8%
Mildly decreased: 60-89 mL/mg/1.73 m2
118
  58.1%
102
  50.2%
220
  54.2%
Mildly to moderately decreased: 45-59 mL/mg/1.73 m2
39
  19.2%
41
  20.2%
80
  19.7%
Moderately to severely decreased: 30-44 mL/mg/1.73 m2
18
   8.9%
28
  13.8%
46
  11.3%
Severely decreased: 15-29 mL/mg/1.73 m2
1
   0.5%
1
   0.5%
2
   0.5%
Missing
3
   1.5%
3
   1.5%
6
   1.5%
1.Primary Outcome
Title Overall Survival
Hide Description OS measures the time from randomization to death due to any cause.
Time Frame 826 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Median (95% Confidence Interval)
Unit of Measure: days
303
(209 to 400)
303
(248 to 346)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8275
Comments P-value stratified by cytogenetic risk factor and ECOG performance status
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Morphologic Complete Remission (CR) Rate
Hide Description

The CR rate is the proportion of patients who achieve a morphologic CR according to the response criteria

  • <5% blasts in a bone marrow aspirate sample with spicules
  • There should be no blasts with Auer rods
  • No EMD
  • Absolute Neutrophil Count (ANC) ≥1,000/μL
  • Platelet count of ≥100,000/μL
  • Patient must be independent of transfusions (for at least 1week before each assessment)
Time Frame 744 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Measure Type: Count of Participants
Unit of Measure: Participants
24
  11.8%
35
  17.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1244
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Secondary Outcome
Title Complete Remission Without Minimal Residual Disease (CRmrd) Rate
Hide Description

proportion of patients who achieve a CR without minimal residual disease by multicolor flow cytometry according to the following criteria

  • Morphologic CR
  • Minimal Residual Disease (MRD) by MFC negative
Time Frame 826 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Measure Type: Count of Participants
Unit of Measure: Participants
12
   5.9%
20
   9.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1430
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Cytogenetic Complete Remission (CRc) Rate
Hide Description

The CRc rate is the proportion of patients who achieve a reversion to a normal karyotype at CR within the study period. This endpoint applies only to patients with abnormal cytogenetic at enrollment according to the following criterion

Morphologic CR plus reversion to a normal karyotype (defined as no clonal abnormalities detected in a minimum of 20 mitotic cells)

Time Frame 826 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 80 64
Measure Type: Count of Participants
Unit of Measure: Participants
7
   8.8%
8
  12.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9977
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Transfusion Independence (TI)
Hide Description Transfusion independence rate is defined as the proportion of patients who show eight weeks or over without red blood cell (RBC-TI) and/or platelet (PLT-TI) transfusion during study period
Time Frame 826 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Measure Type: Count of Participants
Unit of Measure: Participants
81
  39.9%
81
  39.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9959
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
6.Other Pre-specified Outcome
Title Composite Complete Remission (cCR) Rate
Hide Description Composite complete remission (cCR) rate is the proportion of patients who achieve either a disease response of CR, CRi or MLFS (i.e., cCR = CR + CRi + MLFS) within the study period, according to the response criteria
Time Frame 744 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Measure Type: Count of Participants
Unit of Measure: Participants
73
  36.0%
64
  31.5%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3502
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Other Pre-specified Outcome
Title Duration of Composite Complete Remission
Hide Description Duration of cCR response is the time from first cCR until documented relapse (the definition of relapse from CR will be applied) or death. Duration of cCR is only defined for patients who achieve a cCR
Time Frame 744 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 73 64
Median (95% Confidence Interval)
Unit of Measure: days
576 [1] 
(276 to NA)
319
(170 to 744)
[1]
The upper confidence limit for median cannot be estimated (and it was reported as NA) as the curve that represents the upper confidence limits for the survivor function lies above 0.50. The LogLog transformation was used for computing the confidence interval
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0502
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
8.Other Pre-specified Outcome
Title Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30)
Hide Description QLQ-C30 is made of multi-item scales and single-item measures (functional and symptom scales, a global health status/QoL scale and single items). Item range is the difference between possible max and min response to individual items of the scale; most items take values from 1 to 4 (range=3). Global health status takes values from 1 to 7 (range = 6). For statistical analysis purpose, single-item and scale values were all standardized (according to linear transformation described in Scoring Manual) to obtain scores ranging 0-100. An high scale score represents an higher response level. Thus an high score for a functional scale represents an high/healthy level of functioning, an high score for the global health status/QoL represents a high QoL, an high score for a symptom scale/item represents an high level of symptomatology/problems.
Time Frame from baseline up to 660 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Mean (Standard Deviation)
Unit of Measure: score on a scale
Global Health Status -7.040  (31.4458) -2.303  (28.6611)
Functional Scale - Physical Functioning -8.937  (32.1163) -7.018  (25.8512)
Functional Scale - Role Functioning -6.034  (46.3793) -2.000  (40.2659)
Symptom Scale - Fatigue 2.107  (34.2928) 4.240  (29.7030)
Symptom Scale - Nausea and Vomiting 5.460  (28.1649) 5.263  (23.2870)
Symptom Scale - Appetite Loss 9.771  (42.8107) 3.509  (40.2150)
9.Other Pre-specified Outcome
Title Relapse Free Survival
Hide Description the time from the date of achievement of CR or CRi until the date of relapse or death from any cause
Time Frame 744 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Median (95% Confidence Interval)
Unit of Measure: days
291
(217 to 429)
190
(155 to 319)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4656
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
10.Other Pre-specified Outcome
Title Progressive Free Survival Rate (PFS)
Hide Description PFS is defined as the time from the date of randomization until the date of relapse (progression), or death from any cause, whichever occurs first.
Time Frame 800 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Median (95% Confidence Interval)
Unit of Measure: days
217
(126 to 257)
220
(182 to 271)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7063
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
11.Other Pre-specified Outcome
Title Duration of Morphologic CR
Hide Description Duration of morphologic CR is defined as the time from the date of achievement of CR until the date of relapse (progression).
Time Frame 744 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 24 35
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(352 to NA)
319
(119 to 744)
[1]
Median was not reachable due to low number of patients with events (CR) therefore the upper limit is not computable
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0592
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
12.Other Pre-specified Outcome
Title Time to CR
Hide Description Time to CR is defined as the time from the date of randomization until the date of CR in the absence of interceding therapies. The analysis set was the ITT set.
Time Frame 616 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
361 [2] 
(311 to NA)
[1]
Time to CR was censored at the date of the last assessment of patient status excluding CR in case no CR occurred by time of analysis. The number of subjects reaching CR was lower than 50%, then neither the median nor the confidence interval were computable
[2]
The upper confidence limit for median cannot be estimated (and it was reported as NA) as the curve that represents the upper confidence limits for the survivor function lies above 0.50. The LogLog transformation was used for computing the confidence interval
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3835
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
13.Other Pre-specified Outcome
Title Morphologic CR Within 6 Cycles Rate
Hide Description Morphologic CR within 6 cycles rate is defined as the proportion of patients who achieved CR in the absence of interceding therapies within 6 treatment cycles (i.e., during treatment phase up to Day 1 of Cycle 7 included). Analysis was performed in the ITT set.
Time Frame within 6 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description:

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

Overall Number of Participants Analyzed 203 203
Measure Type: Number
Unit of Measure: number of patients
14 16
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pracinostat Plus AZA, Placebo Plus AZA
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7099
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Time Frame TEAEs are with onset date/time at or after start date/time of first intake of pracinostat /placebo, or AEs with onset date/time prior to start date/time of first intake of pracinostat/placebo that worsen in severity after start date/time of first intake of pracinostat /placebo, up to end of observation period. Observation period is defined as 30 days after last dose of pracinostat/placebo or start of new therapy for AML whichever occurs first up to 672 days. OS was collected up to 826 days.
Adverse Event Reporting Description

When evaluating all-cause mortality, the population at risk included all the patients randomized (203 patients per each arm) being the mortality linked to the efficacy endpoint.

When evaluating Adverse Events, the population at risk included patients who received at least one dose of treatment (201 patients per each arm).

 
Arm/Group Title Pracinostat Plus AZA Placebo Plus AZA
Hide Arm/Group Description

60 mg capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Pracinostat: 60 mg capsule

Azacitidine: SC or IV injection

1 capsule orally, once a day, 3 times a week for 3 weeks, followed by 1 week of rest of each 28-day cycle. As a background therapy azacitidine (AZA) will be administered at a dose of 75 mg/m2 by SC or IV injection daily for 7 days of each 28-day cycle.

Placebos: capsule

Azacitidine: SC or IV injection

All-Cause Mortality
Pracinostat Plus AZA Placebo Plus AZA
Affected / at Risk (%) Affected / at Risk (%)
Total   121/203 (59.61%)      128/203 (63.05%)    
Hide Serious Adverse Events
Pracinostat Plus AZA Placebo Plus AZA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   153/201 (76.12%)      151/201 (75.12%)    
Blood and lymphatic system disorders     
Febrile neutropenia   60/201 (29.85%)  105 53/201 (26.37%)  79
Anaemia   9/201 (4.48%)  11 9/201 (4.48%)  16
Thrombocytopenia   7/201 (3.48%)  8 5/201 (2.49%)  10
Pancytopenia   5/201 (2.49%)  10 3/201 (1.49%)  5
Neutropenia   1/201 (0.50%)  1 4/201 (1.99%)  4
Cardiac disorders     
Atrial fibrillation   5/201 (2.49%)  6 2/201 (1.00%)  2
Gastrointestinal disorders     
Vomiting   7/201 (3.48%)  7 2/201 (1.00%)  2
Nausea   6/201 (2.99%)  6 0/201 (0.00%)  0
General disorders     
Pyrexia   11/201 (5.47%)  12 15/201 (7.46%)  17
Fatigue   6/201 (2.99%)  7 2/201 (1.00%)  2
Infections and infestations     
Pneumonia   25/201 (12.44%)  27 31/201 (15.42%)  37
Sepsis   18/201 (8.96%)  20 15/201 (7.46%)  17
Urinary tract infection   9/201 (4.48%)  16 6/201 (2.99%)  6
Cellulitis   5/201 (2.49%)  5 5/201 (2.49%)  5
Septic shock   5/201 (2.49%)  5 4/201 (1.99%)  4
Lung infection   5/201 (2.49%)  5 3/201 (1.49%)  3
Bacteraemia   5/201 (2.49%)  6 2/201 (1.00%)  2
Neutropenic sepsis   4/201 (1.99%)  6 1/201 (0.50%)  1
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications   3/201 (1.49%)  3 6/201 (2.99%)  7
Investigations     
Investigations   8/201 (3.98%)  9 3/201 (1.49%)  3
Metabolism and nutrition disorders     
Metabolism and nutrition disorders   10/201 (4.98%)  12 5/201 (2.49%)  5
Nervous system disorders     
Nervous system disorders   10/201 (4.98%)  11 9/201 (4.48%)  10
Renal and urinary disorders     
Renal and urinary disorders   3/201 (1.49%)  3 6/201 (2.99%)  6
Respiratory, thoracic and mediastinal disorders     
Epistaxis   5/201 (2.49%)  9 0/201 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders   0/201 (0.00%)  0 6/201 (2.99%)  7
Vascular disorders     
Vascular disorders   8/201 (3.98%)  8 5/201 (2.49%)  7
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Pracinostat Plus AZA Placebo Plus AZA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   197/201 (98.01%)      193/201 (96.02%)    
Blood and lymphatic system disorders     
Anaemia   59/201 (29.35%)  126 69/201 (34.33%)  158
Febrile neutropenia   69/201 (34.33%)  123 61/201 (30.35%)  97
Thrombocytopenia   44/201 (21.89%)  97 41/201 (20.40%)  88
Neutropenia   37/201 (18.41%)  63 32/201 (15.92%)  68
Cardiac disorders     
Cardiac disorders   41/201 (20.40%)  59 39/201 (19.40%)  58
Atrial fibrillation   17/201 (8.46%)  23 13/201 (6.47%)  16
Gastrointestinal disorders     
Nausea   85/201 (42.29%)  125 79/201 (39.30%)  101
Vomiting   64/201 (31.84%)  96 50/201 (24.88%)  80
Constipation   56/201 (27.86%)  76 60/201 (29.85%)  76
Diarrhoea   54/201 (26.87%)  83 35/201 (17.41%)  52
Abdominal pain   16/201 (7.96%)  18 15/201 (7.46%)  17
Haemorrhoids   16/201 (7.96%)  18 11/201 (5.47%)  13
Proctalgia   10/201 (4.98%)  12 6/201 (2.99%)  7
Mouth ulceration   12/201 (5.97%)  13 5/201 (2.49%)  5
Oral candidiasis   11/201 (5.47%)  13 11/201 (5.47%)  11
General disorders     
Pyrexia   43/201 (21.39%)  68 45/201 (22.39%)  76
Fatigue   37/201 (18.41%)  44 38/201 (18.91%)  48
Oedema peripheral   29/201 (14.43%)  42 31/201 (15.42%)  37
Asthenia   24/201 (11.94%)  32 17/201 (8.46%)  19
Infections and infestations     
Pneumonia   36/201 (17.91%)  39 44/201 (21.89%)  54
Urinary tract infection   21/201 (10.45%)  29 18/201 (8.96%)  23
Sepsis   18/201 (8.96%)  20 15/201 (7.46%)  17
Upper respiratory tract infection   17/201 (8.46%)  19 7/201 (3.48%)  8
Injury, poisoning and procedural complications     
Injury, poisoning and procedural complications   36/201 (17.91%)  65 46/201 (22.89%)  62
Transfusion reaction   10/201 (4.98%)  20 4/201 (1.99%)  6
Fall   10/201 (4.98%)  12 6/201 (2.99%)  6
Investigations     
Investigations   74/201 (36.82%)  223 60/201 (29.85%)  108
Platelet count decreased   23/201 (11.44%)  69 7/201 (3.48%)  8
Neutrophil count decreased   16/201 (7.96%)  46 13/201 (6.47%)  18
Weight decreased   24/201 (11.94%)  26 15/201 (7.46%)  15
Metabolism and nutrition disorders     
Hypokalaemia   48/201 (23.88%)  80 39/201 (19.40%)  60
Decreased appetite   39/201 (19.40%)  52 31/201 (15.42%)  35
Hypomagnesaemia   20/201 (9.95%)  23 19/201 (9.45%)  38
Hypophosphataemia   17/201 (8.46%)  18 9/201 (4.48%)  10
Hyperglycaemia   12/201 (5.97%)  12 11/201 (5.47%)  11
Hyponatraemia   10/201 (4.98%)  12 7/201 (3.48%)  8
Musculoskeletal and connective tissue disorders     
Musculoskeletal and connective tissue disorders   41/201 (20.40%)  79 59/201 (29.35%)  86
Back pain   10/201 (4.98%)  17 23/201 (11.44%)  24
Pain in extremity   12/201 (5.97%)  12 9/201 (4.48%)  9
Nervous system disorders     
Nervous system disorders   61/201 (30.35%)  88 62/201 (30.85%)  84
Dizziness   13/201 (6.47%)  14 22/201 (10.95%)  26
Headache   14/201 (6.97%)  20 12/201 (5.97%)  13
Psychiatric disorders     
Psychiatric disorders   35/201 (17.41%)  47 40/201 (19.90%)  47
Insomnia   15/201 (7.46%)  18 7/201 (3.48%)  9
Renal and urinary disorders     
Renal and urinary disorders   32/201 (15.92%)  46 50/201 (24.88%)  68
Acute kidney injury   13/201 (6.47%)  13 12/201 (5.97%)  14
Respiratory, thoracic and mediastinal disorders     
Respiratory, thoracic and mediastinal disorders   73/201 (36.32%)  138 85/201 (42.29%)  159
Dyspnoea   15/201 (7.46%)  18 28/201 (13.93%)  29
Epistaxis   20/201 (9.95%)  28 13/201 (6.47%)  18
Cough   17/201 (8.46%)  20 20/201 (9.95%)  23
Pleural effusion   8/201 (3.98%)  9 13/201 (6.47%)  13
Skin and subcutaneous tissue disorders     
Skin and subcutaneous tissue disorders   56/201 (27.86%)  89 57/201 (28.36%)  100
Rash   12/201 (5.97%)  14 10/201 (4.98%)  11
Vascular disorders     
Vascular disorders   54/201 (26.87%)  72 39/201 (19.40%)  50
Hypertension   13/201 (6.47%)  14 15/201 (7.46%)  18
Hypotension   17/201 (8.46%)  20 11/201 (5.47%)  11
Haematoma   10/201 (4.98%)  10 1/201 (0.50%)  1
Indicates events were collected by systematic assessment
Results of the interim analysis (OS curves crossing at about 300 days) demonstrated futility according to the planned threshold and concluded that it was unlikely to meet the primary endpoint compared to the control group at the final analysis. Based on this outcome, the decision taken was to discontinue the recruitment of patients and terminate the study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Francesco Scarci
Organization: Helsinn Healthcare SA
Phone: +41 (0)91 985 1946
EMail: francesco.scarci@helsinn.com
Layout table for additonal information
Responsible Party: Helsinn Healthcare SA
ClinicalTrials.gov Identifier: NCT03151408    
Other Study ID Numbers: PRAN-16-52
First Submitted: May 5, 2017
First Posted: May 12, 2017
Results First Submitted: August 20, 2021
Results First Posted: March 10, 2022
Last Update Posted: March 10, 2022