Acute Myeloid Leukemia
Conditions
Keywords
AML
Brief summary
This is a Phase III, multicenter, double-blind, randomized study of pracinostat vs. placebo with azacitidine (AZA) as background therapy in patients ≥ 18 years of age with newly diagnosed acute myeloid leukemia (AML), excluding acute promyelocytic leukemia and cytogenetic low-risk AML, who are unfit to receive intensive remission induction chemotherapy due to age ≥ 75 years or comorbidities. Patients will be randomized in a 1:1 ratio to one of two groups: Group A (experimental group) to receive pracinostat plus AZA and Group B (control group) to receive placebo plus AZA. Randomization will be stratified by cytogenetic risk category (intermediate vs. unfavorable-risk, according to SWOG Cytogenetic Risk Category Definitions) and ECOG performance status (0-1 vs. 2). Treatments will be administered based on 28-day cycles, with pracinostat/placebo administered orally once every other day, 3 times a week for 3 weeks, followed by one week of no treatment and AZA administered for 7 days of each cycle. Study treatment should continue until there is documented disease progression, relapse from complete remission (CR), or non-manageable toxicity. A minimum of 6 cycles may be required to achieve a complete remission. Once permanently discontinued from study treatment, patients will enter the Long-term Follow-up phase of the study and will be followed for assessment of disease progression, if applicable, and survival every 3 months (±1 month) until death. The end of this study is defined when 390 events (deaths) have occurred and the study is unblinded for final overall survival analysis. Patients who are receiving study treatment at the end of the study may have the opportunity to continue to receive the study drugs to which they were randomized to (Post- Study Observation Period), until the Sponsor informs the Investigators of the appropriate course of action based on the study results. The Post-Study Observation Period is defined as the period starting from the end of the study for a maximum of 12 months.
Interventions
Sponsors
Clinipace Worldwide
Helsinn Healthcare SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patient ≥ 18 years of age with newly diagnosed, histologically or cytologically confirmed, AML including de novo, secondary to antecedent hematologic disorders, or treatment-related disease with intermediate or unfavorable-risk cytogenetics 2. Unable to receive intensive chemotherapy regimens at enrollment, based on one of the following: I. Age ≥ 75 years, or II. Age \< 75 years with at least 1 of the following co-morbidities: 1. An ECOG performance status of 2 2. Clinically significant cardiovascular disease defined as: i. Left ventricular ejection fraction (LVEF) ≤ 50%, measured within 3 months prior to Day 1 confirmed by ECHO/MUGA ii. Congestive heart failure requiring medical therapy iii. Chronic stable angina requiring medical therapy iv. Prior cerebrovascular accident with sequelae c. Clinically significant pulmonary disease defined as: i. Forced expiratory volume in 1 second (FEV1) ≤ 65% of expected ii. Lung diffusing capacity for carbon monoxide (DLCO) ≤ 65% of expected Confirmed by pulmonary tests. d. Diabetes mellitus with symptomatic end-organ damage (e.g., retinopathy, nephropathy, neuropathy, vasculopathy) e. Autoimmune inflammatory conditions (e.g., rheumatoid arthritis, systemic lupus erythematous, inflammatory bowel disease, or similar) requiring chronic disease modifying therapy (e.g., etanercept, adalimumab, infliximab, rituximab, methotrexate, or similar) f. Class III obesity defined as a Body Mass Index (BMI) \> 40 kg/m2 g. Renal impairment defined as serum creatinine \> 1.3 mg/dL (\> 115 µmol/L) or creatinine clearance \<70 ml/min h. Clinically significant cognitive impairment defined as requiring medical therapy and/or assistance with activities of daily living 3. 20% blasts in bone marrow 4. Peripheral white blood cell (WBC) count 30,000/µL For cyto-reduction, hydroxyurea is allowed during screening and up to Cycle 1, Days 1-14, to reduce WBC count to \< 30,000 µL prior to Day 1. After Cycle 1, Day 14, hydroxyurea is prohibited. 5. ECOG performance status ≤ 2 6. Adequate organ function as evidenced by the following laboratory findings: 1. Total bilirubin ≤ 2 × upper limit of normal (ULN) or \< 3 x ULN for patients with Gilbert-Meulengracht Syndrome 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN 7. Serum creatinine ≤ 1.5 × ULN according to institutional standards or creatinine clearance ≥ 50 mL/min 8. QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 ms on electrocardiogram (ECG) at Screening 9. Male patient who is surgically sterile, or male patient who is willing to agree to remain completely abstinent (refrain from heterosexual intercourse) or who use barrier contraceptive measures and agree to refrain from donating sperm during the entire study treatment period and for 3 months after the last administration of study drug 10. Female patient who is of childbearing potential willing to use adequate contraceptive measures while participating on study, OR willing to completely abstain from heterosexual intercourse during the entire study treatment period 11. Female patient who is of childbearing potential must have a negative serum pregnancy test result within 3 weeks prior to starting study drugs. 12. Willing to provide voluntary written informed consent before performance of any study related procedure not part of normal medical care 13. Willing and able to understand the nature of this study and to comply with the study and follow-up procedures.
Exclusion criteria
1. Able to receive intensive induction chemotherapy 2. AML-associated inv(16)/t(16;16)/del(16q), t(15;17) (i.e. promyelocytic leukemia) with/without secondary aberrations; t(8;21) lacking del (9q) or complex karyotypes 3. Presence of an active malignant disease within the last 12 months, with the exception of adequately treated cervical cancer in-situ, non-melanoma skin cancer and superficial bladder tumors (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\] and T1 \[tumor invades lamina propria\]). Other malignancies may be considered after consultation with the Medical Monitor 4. Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction that, in the Investigator's opinion, could compromise the patient's safety or put the study outcomes at risk 5. Uncontrolled arrhythmias; any Class 3-4 cardiac diseases as defined by the New York Heart Association (NYHA) functional classification 6. Evidence of AML central nervous system (CNS) involvement 7. Previous chemotherapy for AML except for the following, which are allowed: 1. Hydroxyurea for cytoreduction 2. One course of hypomethylating agent therapy (i.e.; up to 7 doses of azacitidine or 3-5 days of decitabine) within 30 days prior to enrollment (Day 1) 8. Use of experimental drugs ≤ 30 days prior to screening 9. Received prior HDAC inhibitor therapy 10. Received prior treatment with a hypomethylating agent, except as allowed in Exclusion Criterion 7.b 11. Known hypersensitivity to any components of pracinostat, azacitidine, or mannitol 12. History of human immunodeficiency virus (HIV) or an active and uncontrolled infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) 13. Gastrointestinal (GI) tract disease that causes an inability to take oral medication, malabsorption syndrome, or a requirement for IV alimentation; prior surgical procedures affecting absorption; or uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis) 14. Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition, that contraindicates the use of pracinostat and/or AZA, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient inappropriate for this study 15. Breast-feeding woman 16. current smokers(use of patches, chewing gums and vaping nicotine conaining fluids is permitted). Patients who stopped smoking at least 8 day prior to first pracinostat dosing can be enrolled, provided they refrain from smoking during the whole study 17. prohibited concomitant medications 18. uncontrolled infections 19. receive more than 1 prior cycle of HMA or bone marrow transplant for any prior hematological disorder antecedent to AML
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 826 days | OS measures the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Morphologic Complete Remission (CR) Rate | 744 days | 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) |
| Complete Remission Without Minimal Residual Disease (CRmrd) Rate | 826 days | 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 |
| Cytogenetic Complete Remission (CRc) Rate | 826 days | 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) |
| Transfusion Independence (TI) | 826 days | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Morphologic CR | 744 days | Duration of morphologic CR is defined as the time from the date of achievement of CR until the date of relapse (progression). |
| Composite Complete Remission (cCR) Rate | 744 days | 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 |
| Morphologic CR Within 6 Cycles Rate | within 6 cycles | 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 to CR | 616 days | 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. |
| Duration of Composite Complete Remission | 744 days | 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 |
| Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | from baseline up to 660 days | 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. |
| Relapse Free Survival | 744 days | the time from the date of achievement of CR or CRi until the date of relapse or death from any cause |
| Progressive Free Survival Rate (PFS) | 800 days | 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. |
Countries
Argentina, Australia, Austria, Brazil, Czechia, France, Germany, Hungary, Italy, Poland, Romania, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Pracinostat Plus AZA 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 | 203 |
| Placebo Plus AZA 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 | 203 |
| Total | 406 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 24 | 23 |
| Overall Study | Death | 46 | 26 |
| Overall Study | non-compliance by patient | 1 | 0 |
| Overall Study | other reasons | 56 | 52 |
| Overall Study | Physician Decision | 13 | 19 |
| Overall Study | Progressive disease | 45 | 61 |
| Overall Study | randomized and not treated | 2 | 2 |
| Overall Study | Withdrawal by Subject | 16 | 20 |
Baseline characteristics
| Characteristic | Pracinostat Plus AZA | Placebo Plus AZA | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 196 Participants | 198 Participants | 394 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Continuous | 75.4 years STANDARD_DEVIATION 5.48 | 75.1 years STANDARD_DEVIATION 5.91 | 75.3 years STANDARD_DEVIATION 5.69 |
| Cytogenetic Risk Category (central Lab results) Intermediate | 109 Participants | 107 Participants | 216 Participants |
| Cytogenetic Risk Category (central Lab results) Missing | 43 Participants | 36 Participants | 79 Participants |
| Cytogenetic Risk Category (central Lab results) Unfavorable | 51 Participants | 60 Participants | 111 Participants |
| Cytogenetic Risk Category (local or central Lab results used for randomization) Intermediate | 136 Participants | 135 Participants | 271 Participants |
| Cytogenetic Risk Category (local or central Lab results used for randomization) unfavorable | 67 Participants | 68 Participants | 135 Participants |
| ECOG PS (at cycle 1 Day 1) Grade 0-1 | 114 Participants | 110 Participants | 224 Participants |
| ECOG PS (at cycle 1 Day 1) Grade 2 | 85 Participants | 88 Participants | 173 Participants |
| ECOG PS (at cycle 1 Day 1) Grade 3 | 0 Participants | 1 Participants | 1 Participants |
| ECOG PS (at cycle 1 Day 1) Missing | 4 Participants | 4 Participants | 8 Participants |
| ECOG PS (used for randomization) Grade 0-1 | 113 Participants | 114 Participants | 227 Participants |
| ECOG PS (used for randomization) Grade 2 | 90 Participants | 89 Participants | 179 Participants |
| Height | 165.1 cm STANDARD_DEVIATION 10.23 | 165.7 cm STANDARD_DEVIATION 8.96 | 165.4 cm STANDARD_DEVIATION 9.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 26 Participants | 53 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 22 Participants | 28 Participants | 50 Participants |
| Race (NIH/OMB) White | 149 Participants | 140 Participants | 289 Participants |
| Region of Enrollment Argentina | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment Australia | 34 Participants | 29 Participants | 63 Participants |
| Region of Enrollment Austria | 4 Participants | 6 Participants | 10 Participants |
| Region of Enrollment Brazil | 10 Participants | 15 Participants | 25 Participants |
| Region of Enrollment Czechia | 10 Participants | 8 Participants | 18 Participants |
| Region of Enrollment France | 8 Participants | 10 Participants | 18 Participants |
| Region of Enrollment Germany | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment Hungary | 12 Participants | 14 Participants | 26 Participants |
| Region of Enrollment Italy | 19 Participants | 11 Participants | 30 Participants |
| Region of Enrollment Poland | 21 Participants | 13 Participants | 34 Participants |
| Region of Enrollment Romania | 10 Participants | 7 Participants | 17 Participants |
| Region of Enrollment South Korea | 8 Participants | 7 Participants | 15 Participants |
| Region of Enrollment Spain | 24 Participants | 28 Participants | 52 Participants |
| Region of Enrollment Taiwan | 17 Participants | 18 Participants | 35 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 11 Participants | 17 Participants |
| Region of Enrollment United States | 12 Participants | 18 Participants | 30 Participants |
| Renal impairment Mildly decreased: 60-89 mL/mg/1.73 m2 | 118 Participants | 102 Participants | 220 Participants |
| Renal impairment Mildly to moderately decreased: 45-59 mL/mg/1.73 m2 | 39 Participants | 41 Participants | 80 Participants |
| Renal impairment Missing | 3 Participants | 3 Participants | 6 Participants |
| Renal impairment Moderately to severely decreased: 30-44 mL/mg/1.73 m2 | 18 Participants | 28 Participants | 46 Participants |
| Renal impairment Normal or high: ≥ 90 mL/mg/1.73 m2 | 24 Participants | 28 Participants | 52 Participants |
| Renal impairment Severely decreased: 15-29 mL/mg/1.73 m2 | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 87 Participants | 87 Participants | 174 Participants |
| Sex: Female, Male Male | 116 Participants | 116 Participants | 232 Participants |
| Smoking Habits Current smoker | 0 Participants | 3 Participants | 3 Participants |
| Smoking Habits Ex-smoker | 73 Participants | 79 Participants | 152 Participants |
| Smoking Habits Non-smoker | 130 Participants | 121 Participants | 251 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 121 / 203 | 128 / 203 |
| other Total, other adverse events | 197 / 201 | 193 / 201 |
| serious Total, serious adverse events | 153 / 201 | 151 / 201 |
Outcome results
Primary
Overall Survival
OS measures the time from randomization to death due to any cause.
Time frame: 826 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pracinostat Plus AZA | Overall Survival | 303 days |
| Placebo Plus AZA | Overall Survival | 303 days |
p-value: 0.8275Log Rank
Secondary
Complete Remission Without Minimal Residual Disease (CRmrd) Rate
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pracinostat Plus AZA | Complete Remission Without Minimal Residual Disease (CRmrd) Rate | 12 Participants |
| Placebo Plus AZA | Complete Remission Without Minimal Residual Disease (CRmrd) Rate | 20 Participants |
p-value: 0.143Cochran-Mantel-Haenszel
Secondary
Cytogenetic Complete Remission (CRc) Rate
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pracinostat Plus AZA | Cytogenetic Complete Remission (CRc) Rate | 7 Participants |
| Placebo Plus AZA | Cytogenetic Complete Remission (CRc) Rate | 8 Participants |
p-value: 0.9977Cochran-Mantel-Haenszel
Secondary
Morphologic Complete Remission (CR) Rate
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pracinostat Plus AZA | Morphologic Complete Remission (CR) Rate | 24 Participants |
| Placebo Plus AZA | Morphologic Complete Remission (CR) Rate | 35 Participants |
p-value: 0.1244Cochran-Mantel-Haenszel
Secondary
Transfusion Independence (TI)
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pracinostat Plus AZA | Transfusion Independence (TI) | 81 Participants |
| Placebo Plus AZA | Transfusion Independence (TI) | 81 Participants |
p-value: 0.9959Cochran-Mantel-Haenszel
Other Pre-specified
Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30)
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pracinostat Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Global Health Status | -7.040 score on a scale | Standard Deviation 31.4458 |
| Pracinostat Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Functional Scale - Physical Functioning | -8.937 score on a scale | Standard Deviation 32.1163 |
| Pracinostat Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Functional Scale - Role Functioning | -6.034 score on a scale | Standard Deviation 46.3793 |
| Pracinostat Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Symptom Scale - Fatigue | 2.107 score on a scale | Standard Deviation 34.2928 |
| Pracinostat Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Symptom Scale - Nausea and Vomiting | 5.460 score on a scale | Standard Deviation 28.1649 |
| Pracinostat Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Symptom Scale - Appetite Loss | 9.771 score on a scale | Standard Deviation 42.8107 |
| Placebo Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Symptom Scale - Nausea and Vomiting | 5.263 score on a scale | Standard Deviation 23.287 |
| Placebo Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Global Health Status | -2.303 score on a scale | Standard Deviation 28.6611 |
| Placebo Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Symptom Scale - Fatigue | 4.240 score on a scale | Standard Deviation 29.703 |
| Placebo Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Functional Scale - Physical Functioning | -7.018 score on a scale | Standard Deviation 25.8512 |
| Placebo Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Symptom Scale - Appetite Loss | 3.509 score on a scale | Standard Deviation 40.215 |
| Placebo Plus AZA | Change in Quality of Life From Baseline (EORTC QLQ-C30 - European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30) | Functional Scale - Role Functioning | -2.000 score on a scale | Standard Deviation 40.2659 |
Other Pre-specified
Composite Complete Remission (cCR) Rate
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pracinostat Plus AZA | Composite Complete Remission (cCR) Rate | 73 Participants |
| Placebo Plus AZA | Composite Complete Remission (cCR) Rate | 64 Participants |
p-value: 0.3502Cochran-Mantel-Haenszel
Other Pre-specified
Duration of Composite Complete Remission
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pracinostat Plus AZA | Duration of Composite Complete Remission | 576 days |
| Placebo Plus AZA | Duration of Composite Complete Remission | 319 days |
p-value: 0.0502Log Rank
Other Pre-specified
Duration of Morphologic CR
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pracinostat Plus AZA | Duration of Morphologic CR | NA days |
| Placebo Plus AZA | Duration of Morphologic CR | 319 days |
p-value: 0.0592Log Rank
Other Pre-specified
Morphologic CR Within 6 Cycles Rate
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pracinostat Plus AZA | Morphologic CR Within 6 Cycles Rate | 14 number of patients |
| Placebo Plus AZA | Morphologic CR Within 6 Cycles Rate | 16 number of patients |
p-value: 0.7099Cochran-Mantel-Haenszel
Other Pre-specified
Progressive Free Survival Rate (PFS)
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pracinostat Plus AZA | Progressive Free Survival Rate (PFS) | 217 days |
| Placebo Plus AZA | Progressive Free Survival Rate (PFS) | 220 days |
p-value: 0.7063Log Rank
Other Pre-specified
Relapse Free Survival
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pracinostat Plus AZA | Relapse Free Survival | 291 days |
| Placebo Plus AZA | Relapse Free Survival | 190 days |
p-value: 0.4656Log Rank
Other Pre-specified
Time to CR
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pracinostat Plus AZA | Time to CR | NA days |
| Placebo Plus AZA | Time to CR | 361 days |
p-value: 0.3835Log Rank