An Efficacy and Safety Study of Decitabine (DACOGEN) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus Decitabine (DACOGEN) Alone in Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02472145
Collaborator
(none)
326
81
2
29.7
4
0.1
Study Details
Study Description
Brief Summary
The primary objective of study Part A is to assess the safety of talacotuzumab (formerly CSL362) monotherapy and confirm the recommended Phase 2 dose (RP2D) in participants with acute myeloid leukemia (AML) for whom experimental therapy is appropriate. The primary objective of study Part B are to assess complete response (CR) rate and overall survival (OS) in participants with AML who are not eligible for intense induction chemotherapy and who are randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Detailed Description
This is a 2-part, open-label, multicenter, Phase 2/3 study conducted in participants with AML who are suitable for experimental therapy (Part A) and in participants with untreated AML who are not eligible for intense induction chemotherapy or hematopoeitic stem cell transplantation (HSCT) (Part B). In Study Part A, the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile will be assessed to confirm the RP2D of 9 milligram per kilogram (mg/kg) talacotuzumab. In Study Part B, participants will be randomized in a 1:1 ratio into either decitabine + talacotuzumab (arm 1) or decitabine alone (arm 2). Blood and bone marrow sampling will be done in Part A and B for disease assessment, PK, PD, and biomarkers will be collected in all participants. Safety will be monitored throughout the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
326 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase 2/3 Study of DACOGEN® (Decitabine) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus DACOGEN (Decitabine) Alone in Patients With AML Who Are Not Candidates for Intensive Chemotherapy
Actual Study Start Date
:
Aug 4, 2015
Actual Primary Completion Date
:
Jan 25, 2018
Actual Study Completion Date
:
Jan 25, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Decitabine plus Talacotuzumab Part A: For Cycle 1 of Part A, participants will receive talacotuzumab on Day 1. Starting from Cycle 2 of Part A, participants may receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle. Part B Arm 1: Participants will receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle. |
Drug: Decitabine 20 mg/m^2
Decitabine 20 milligram per square meter (mg/[m^2]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.
Other Names:
Drug: Talacotuzumab 9 mg/kg
Talacotuzumab 9 milligram per kilogram mg/kg on Day 8 and 22 of a 28-day cycle.
Other Names:
|
| Active Comparator: Decitabine Participants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle. |
Drug: Decitabine 20 mg/m^2
Decitabine 20 milligram per square meter (mg/[m^2]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment [Approximately up to 2.5 years]
Complete response rate defined as percentage of participants who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/micro liter [mcL]); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
- Part B: Overall Survival [Approximately up to 2.5 years]
Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. This endpoint is reported here for Part B only as per the planned analysis.
Secondary Outcome Measures
- Part B: Event-free Survival (EFS) Based on Investigator Assessment [Approximately up to 2.5 years]
EFS defined as time from randomization to treatment failure, relapse from CR/CRi, or death from any cause, whichever occurs first, per modified IWG criteria. Treatment failure: >25% absolute increase in the bone marrow blast count from baseline to present assessment (example, 20% to 46%) on bone marrow aspirate (or biopsy in case of dry tap); Relapse: Bone marrow blasts greater than equal to (>=)5%; reappearance of blasts in blood; or development of extramedullary disease; CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL);independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. Endpoint reported is for Part B only as per planned analysis.
- Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate) [Approximately up to 2.5 years]
Percentage of participants who achieved CR and CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/ mcL); platelet count >100 *10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
- Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi) [Approximately 2.5 years]
Percentage of participants who achieved CR plus MRD-negative CRi were reported. MRD negativity defined as <1 blast or leukemic stem cell in 10,000 leukocytes (MRD level <10^4).CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
- Part B: Time to Best Response [Approximately 2.5 years]
Time to best response is calculated as the time from the randomization date to the first documented date for the best response for participants who achieved CR or CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
- Part B: Duration of Response (DOR) Based on Investigator Assessment [Approximately 2.5 years]
DOR defined as number of weeks from documented best response (CR or CRi) for participants who achieved CR or CRi to relapse, death due to relapse, date of censoring. As per modified IWG criteria: CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease;absolute neutrophil count >1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0* 10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.
Eligibility Criteria
Criteria
Ages Eligible for Study:
65 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- De novo or secondary acute myeloid leukemia (AML) (post myelodysplastic syndrome [MDS] or myeloproliferative neoplasm [MPN] or after leukemogenic chemotherapy) according to WHO 2008 criteria
For Part A:
- Participants With AML: treatment naive or relapsed for whom experimental therapy is appropriate (as assessed by their treating physician)
For Part B:
-
Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have at least one of the following: congestive heart failure or ejection fraction less than or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter (mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2; prior or current malignancy that does not require concurrent treatment; unresolved infection; comorbidity that, in the Investigator's opinion, makes the participant unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
-
Previously untreated AML (except: emergency leukopheresis and/or hydroxyurea during the screening phase to control hyperleukocytosis but must be discontinued at least one day prior to start of study therapy)
-
Not eligible for an allogeneic hematopoietic stem cell transplantation
-
ECOG Performance Status score of 0, 1 or 2
-
A woman must be either: Not of childbearing potential: postmenopausal (more than [>] 45 years of age with amenorrhea for at least 12 months; If, of childbearing potential must be practicing a highly effective method of birth control
-
A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening
-
A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least 3 months after last study treatment
Exclusion Criteria:
-
Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARalpha)
-
For Part B only: Known leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
-
Participants who received prior treatment with a hypomethylating agent
-
For Part A only: Participants who did not recover from all clinically significant toxicities (excluding alopecia and hematologic toxicities) of any previous surgery, radiotherapy, targeted therapy, or chemotherapy to less than or equal to Grade 1
-
Any uncontrolled active systemic infection that requires treatment with intravenous (IV) antibiotics
-
A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening
-
Active systemic hepatitis infection requiring treatment or other clinically active liver disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orange | California | United States | ||
| 2 | Aurora | Colorado | United States | ||
| 3 | New Orleans | Louisiana | United States | ||
| 4 | Detroit | Michigan | United States | ||
| 5 | Lebanon | New Hampshire | United States | ||
| 6 | New York | New York | United States | ||
| 7 | Rochester | New York | United States | ||
| 8 | Charleston | South Carolina | United States | ||
| 9 | Nashville | Tennessee | United States | ||
| 10 | Dallas | Texas | United States | ||
| 11 | Houston | Texas | United States | ||
| 12 | Herston | Australia | |||
| 13 | Melbourne | Australia | |||
| 14 | Perth | Australia | |||
| 15 | South Woodville | Australia | |||
| 16 | Woolloongabba | Australia | |||
| 17 | Antwerp | Belgium | |||
| 18 | Hasselt | Belgium | |||
| 19 | Leuven | Belgium | |||
| 20 | Liege | Belgium | |||
| 21 | Mons | Belgium | |||
| 22 | Turnhout | Belgium | |||
| 23 | Wilrijk | Belgium | |||
| 24 | Grenoble Cedex 9 | France | |||
| 25 | Lyon Cedex 08 | France | |||
| 26 | Marseille | France | |||
| 27 | Montpellier | France | |||
| 28 | Nantes Cedex 2 | France | |||
| 29 | Paris Cedex 10 | France | |||
| 30 | Toulouse Cedex 9 | France | |||
| 31 | Dresden | Germany | |||
| 32 | Düsseldorf | Germany | |||
| 33 | Essen | Germany | |||
| 34 | Frankfurt/Main | Germany | |||
| 35 | Hamburg | Germany | |||
| 36 | München | Germany | |||
| 37 | Münster | Germany | |||
| 38 | Ulm | Germany | |||
| 39 | Würzburg | Germany | |||
| 40 | Haifa | Israel | |||
| 41 | Jerusalem | Israel | |||
| 42 | Ramat Gan | Israel | |||
| 43 | Tel Aviv | Israel | |||
| 44 | Busan | Korea, Republic of | |||
| 45 | Daegu | Korea, Republic of | |||
| 46 | Hwasun Gun | Korea, Republic of | |||
| 47 | Seoul | Korea, Republic of | |||
| 48 | Katowice | Poland | |||
| 49 | Krakow | Poland | |||
| 50 | Lodz | Poland | |||
| 51 | Lublin | Poland | |||
| 52 | Warszawa | Poland | |||
| 53 | Chelyabinsk | Russian Federation | |||
| 54 | Dzerzhinsk | Russian Federation | |||
| 55 | Ekaterinburg | Russian Federation | |||
| 56 | Moscow | Russian Federation | |||
| 57 | Nizhny Novgorod | Russian Federation | |||
| 58 | Ryazan | Russian Federation | |||
| 59 | Samara | Russian Federation | |||
| 60 | Badalona, Barcelona | Spain | |||
| 61 | Barcelona | Spain | |||
| 62 | Madrid | Spain | |||
| 63 | Pozuelo De Alarcon, Madrid | Spain | |||
| 64 | Salamanca | Spain | |||
| 65 | Sevilla | Spain | |||
| 66 | Valencia | Spain | |||
| 67 | Gothenburg | Sweden | |||
| 68 | Stockholm | Sweden | |||
| 69 | Uppsala | Sweden | |||
| 70 | Örebro | Sweden | |||
| 71 | Chiayi | Taiwan | |||
| 72 | Taichung City | Taiwan | |||
| 73 | Tainan City | Taiwan | |||
| 74 | Taipei City | Taiwan | |||
| 75 | Ankara | Turkey | |||
| 76 | Atakum | Turkey | |||
| 77 | Istanbul | Turkey | |||
| 78 | Izmir | Turkey | |||
| 79 | Bournemouth | United Kingdom | |||
| 80 | Cardiff | United Kingdom | |||
| 81 | Wolverhampton | United Kingdom |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02472145
Other Study ID Numbers:
- CR107273
- 56022473AML2002
- 2015-001611-12
First Posted:
Jun 15, 2015
Last Update Posted:
Mar 19, 2019
Last Verified:
Mar 1, 2019
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part A: Decitabine + JNJ-56022473 | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|---|
| Arm/Group Description | Participants received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Period Title: Overall Study | |||
| STARTED | 10 | 159 | 157 |
| Treated | 10 | 156 | 156 |
| Safety | 10 | 165 | 147 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 10 | 159 | 157 |
Baseline Characteristics
| Arm/Group Title | Part A: Decitabine + JNJ-56022473 | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. | Total of all reporting groups |
| Overall Participants | 10 | 159 | 157 | 326 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
65.4
(10.88)
|
75
(5.6)
|
75.2
(5.32)
|
74.8
(5.91)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
4
40%
|
68
42.8%
|
77
49%
|
149
45.7%
|
| Male |
6
60%
|
91
57.2%
|
80
51%
|
177
54.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
4
2.5%
|
5
3.2%
|
9
2.8%
|
| Not Hispanic or Latino |
10
100%
|
143
89.9%
|
143
91.1%
|
296
90.8%
|
| Unknown or Not Reported |
0
0%
|
12
7.5%
|
9
5.7%
|
21
6.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
14
8.8%
|
11
7%
|
25
7.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
1.3%
|
1
0.6%
|
3
0.9%
|
| White |
10
100%
|
133
83.6%
|
141
89.8%
|
284
87.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
9
5.7%
|
4
2.5%
|
13
4%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Asian |
0
0%
|
14
8.8%
|
11
7%
|
25
7.7%
|
| Black or African American |
0
0%
|
2
1.3%
|
1
0.6%
|
3
0.9%
|
| Hispanic or Latino |
0
0%
|
3
1.9%
|
5
3.2%
|
8
2.5%
|
| Other |
0
0%
|
13
8.2%
|
9
5.7%
|
22
6.7%
|
| White Non-Hispanic |
10
100%
|
127
79.9%
|
131
83.4%
|
268
82.2%
|
| Region of Enrollment (Count of Participants) | ||||
| Australia |
0
0%
|
10
6.3%
|
18
11.5%
|
28
8.6%
|
| Belgium |
3
30%
|
11
6.9%
|
6
3.8%
|
20
6.1%
|
| France |
0
0%
|
6
3.8%
|
2
1.3%
|
8
2.5%
|
| Germany |
0
0%
|
14
8.8%
|
18
11.5%
|
32
9.8%
|
| Israel |
0
0%
|
18
11.3%
|
11
7%
|
29
8.9%
|
| Italy |
0
0%
|
12
7.5%
|
11
7%
|
23
7.1%
|
| Poland |
0
0%
|
13
8.2%
|
11
7%
|
24
7.4%
|
| Russia |
0
0%
|
30
18.9%
|
26
16.6%
|
56
17.2%
|
| Spain |
7
70%
|
17
10.7%
|
19
12.1%
|
43
13.2%
|
| Sweden |
0
0%
|
2
1.3%
|
0
0%
|
2
0.6%
|
| Taiwan, Province Of China |
0
0%
|
8
5%
|
4
2.5%
|
12
3.7%
|
| Turkey |
0
0%
|
2
1.3%
|
5
3.2%
|
7
2.1%
|
| United Kingdom |
0
0%
|
1
0.6%
|
3
1.9%
|
4
1.2%
|
| United States |
0
0%
|
10
6.3%
|
16
10.2%
|
26
8%
|
| Korea, Republic Of |
0
0%
|
5
3.1%
|
7
4.5%
|
12
3.7%
|
Outcome Measures
| Title | Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment |
|---|---|
| Description | Complete response rate defined as percentage of participants who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/micro liter [mcL]); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis. |
| Time Frame | Approximately up to 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT) population is defined as all randomized participants, grouped per treatment assigned by randomization, regardless of the actual treatment received. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 159 | 157 |
| Number [Percentage of participants] |
11.9
119%
|
16.6
10.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part B: Decitabine (Alone), Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Comments | Statistical Analysis 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4747 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.5 | |
| Confidence Interval |
(2-Sided) 95% 0.8 to 2.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part B: Overall Survival |
|---|---|
| Description | Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. This endpoint is reported here for Part B only as per the planned analysis. |
| Time Frame | Approximately up to 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population is defined as all randomized participants, grouped per treatment assigned by randomization, regardless of the actual treatment received. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 159 | 157 |
| Median (95% Confidence Interval) [Months] |
7.26
|
5.36
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part B: Decitabine (Alone), Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Comments | Statistical Analysis 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7817 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.04 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 1.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part B: Event-free Survival (EFS) Based on Investigator Assessment |
|---|---|
| Description | EFS defined as time from randomization to treatment failure, relapse from CR/CRi, or death from any cause, whichever occurs first, per modified IWG criteria. Treatment failure: >25% absolute increase in the bone marrow blast count from baseline to present assessment (example, 20% to 46%) on bone marrow aspirate (or biopsy in case of dry tap); Relapse: Bone marrow blasts greater than equal to (>=)5%; reappearance of blasts in blood; or development of extramedullary disease; CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL);independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. Endpoint reported is for Part B only as per planned analysis. |
| Time Frame | Approximately up to 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population defined as all randomized participants, grouped per treatment assigned by randomization, regardless of actual treatment received. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 159 | 157 |
| Median (95% Confidence Interval) [Months] |
6.24
|
4.50
|
| Title | Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate) |
|---|---|
| Description | Percentage of participants who achieved CR and CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/ mcL); platelet count >100 *10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis. |
| Time Frame | Approximately up to 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population is defined as all randomized participants, grouped per treatment assigned by randomization, regardless of the actual treatment received. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 159 | 157 |
| Number [Percentage of Participants] |
20.1
201%
|
26.8
16.9%
|
| Title | Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi) |
|---|---|
| Description | Percentage of participants who achieved CR plus MRD-negative CRi were reported. MRD negativity defined as <1 blast or leukemic stem cell in 10,000 leukocytes (MRD level <10^4).CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis. |
| Time Frame | Approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population included participants in ITT, among whom MRD negativity was evaluated upon achieving response. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 80 | 80 |
| Number [Percentage of participants] |
13.8
138%
|
21.3
13.4%
|
| Title | Part B: Time to Best Response |
|---|---|
| Description | Time to best response is calculated as the time from the randomization date to the first documented date for the best response for participants who achieved CR or CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis. |
| Time Frame | Approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population included participants in ITT, who achieved CR or CRi. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 32 | 42 |
| Median (Full Range) [Weeks] |
16.71
|
18.14
|
| Title | Part B: Duration of Response (DOR) Based on Investigator Assessment |
|---|---|
| Description | DOR defined as number of weeks from documented best response (CR or CRi) for participants who achieved CR or CRi to relapse, death due to relapse, date of censoring. As per modified IWG criteria: CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease;absolute neutrophil count >1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0* 10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis. |
| Time Frame | Approximately 2.5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population included participants in ITT, who achieved CR or CRi. |
| Arm/Group Title | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. |
| Measure Participants | 32 | 42 |
| Median (95% Confidence Interval) [Weeks] |
23.71
|
NA
|
Adverse Events
| Time Frame | Throughout the study (Up to 2.5 years) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Population defined as randomized participants who received at least one dose of study medication, grouped according to actual treatment received (9 participants from decitabine + JNJ-56022473 arm were grouped in the decitabine alone arm as they received only decitabine and not JNJ 56022473). All-cause mortality is reported here for randomized participants. Serious and Other (Not including Serious) Adverse Events are reported for Safety Population per planned analysis. | |||||
| Arm/Group Title | Part A: Decitabine + JNJ-56022473 | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 | |||
| Arm/Group Description | Participants received 1 dose of JNJ-56022473 (talacotuzumab) at 9 milligram per kilogram (mg/kg) as intravenous (IV) infusion on Day 1 of cycle 1. From cycle 2 onwards, participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. | Participants received decitabine 20 mg/m^2 IV on Days 1 to 5 of each 28-day cycle until treatment failure, relapse from CR or CRi, unacceptable toxicity, or death. | Participants received decitabine 20 milligram per meter square (mg/m^2) IV on Day 1 to Day 5 followed by 9 mg/kg JNJ-56022473 on Day 8 and Day 22 of a 28-day cycle until treatment failure, relapse from complete response/remission (CR) or complete response with incomplete recovery (CRi), unacceptable toxicity, or death. | |||
All Cause Mortality |
||||||
| Part A: Decitabine + JNJ-56022473 | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/10 (100%) | 101/159 (63.5%) | 99/157 (63.1%) | |||
Serious Adverse Events |
||||||
| Part A: Decitabine + JNJ-56022473 | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/10 (90%) | 120/165 (72.7%) | 126/147 (85.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/10 (0%) | 6/165 (3.6%) | 4/147 (2.7%) | |||
| Disseminated Intravascular Coagulation | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Febrile Bone Marrow Aplasia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Febrile Neutropenia | 2/10 (20%) | 36/165 (21.8%) | 40/147 (27.2%) | |||
| Leukocytosis | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Neutropenia | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Pancytopenia | 0/10 (0%) | 2/165 (1.2%) | 2/147 (1.4%) | |||
| Splenomegaly | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Thrombocytopenia | 0/10 (0%) | 5/165 (3%) | 3/147 (2%) | |||
| Cardiac disorders | ||||||
| Acute Myocardial Infarction | 0/10 (0%) | 1/165 (0.6%) | 3/147 (2%) | |||
| Angina Pectoris | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Arrhythmia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Atrial Fibrillation | 0/10 (0%) | 2/165 (1.2%) | 5/147 (3.4%) | |||
| Bradycardia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Cardiac Arrest | 0/10 (0%) | 1/165 (0.6%) | 5/147 (3.4%) | |||
| Cardiac Failure | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Cardiac Failure Acute | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Cardiogenic Shock | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Cardiopulmonary Failure | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Cardiovascular Insufficiency | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Myocardial Ischaemia | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Pericardial Effusion | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Supraventricular Tachycardia | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Tachycardia | 0/10 (0%) | 0/165 (0%) | 3/147 (2%) | |||
| Ear and labyrinth disorders | ||||||
| Ear Pain | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Eye disorders | ||||||
| Diplopia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal Pain Upper | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Acute Abdomen | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Anal Ulcer | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Colitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Colitis Ulcerative | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Constipation | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Diarrhoea | 0/10 (0%) | 3/165 (1.8%) | 2/147 (1.4%) | |||
| Diverticular Perforation | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Diverticulum Intestinal | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Dyspepsia | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Gastritis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Gastritis Erosive | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Gastrointestinal Angiodysplasia | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Gastrointestinal Haemorrhage | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Gastrointestinal Inflammation | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Gastrointestinal Polyp Haemorrhage | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Intestinal Haemorrhage | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Large Intestinal Obstruction | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Mechanical Ileus | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Nausea | 0/10 (0%) | 1/165 (0.6%) | 3/147 (2%) | |||
| Oesophagitis | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Pancreatitis Acute | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Rectal Haemorrhage | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Small Intestinal Obstruction | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Vomiting | 1/10 (10%) | 1/165 (0.6%) | 2/147 (1.4%) | |||
| Gastric Haemorrhage | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Upper Gastrointestinal Haemorrhage | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| General disorders | ||||||
| Asthenia | 0/10 (0%) | 0/165 (0%) | 3/147 (2%) | |||
| Catheter Site Inflammation | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Chest Pain | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Chills | 0/10 (0%) | 0/165 (0%) | 3/147 (2%) | |||
| Death | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Fatigue | 0/10 (0%) | 0/165 (0%) | 3/147 (2%) | |||
| General Physical Health Deterioration | 1/10 (10%) | 6/165 (3.6%) | 4/147 (2.7%) | |||
| Hyperthermia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Influenza Like Illness | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Malaise | 0/10 (0%) | 1/165 (0.6%) | 2/147 (1.4%) | |||
| Multiple Organ Dysfunction Syndrome | 0/10 (0%) | 9/165 (5.5%) | 9/147 (6.1%) | |||
| Pyrexia | 1/10 (10%) | 9/165 (5.5%) | 15/147 (10.2%) | |||
| Sudden Death | 0/10 (0%) | 5/165 (3%) | 1/147 (0.7%) | |||
| Condition Aggravated | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholangitis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Cholangitis Acute | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Cholecystitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Cholecystitis Acute | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Immune system disorders | ||||||
| Anaphylactic Reaction | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Anaphylactic Shock | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Serum Sickness | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Infections and infestations | ||||||
| Actinomycotic Pulmonary Infection | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Alveolar Osteitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Anal Infection | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Aspergillus Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Bacteraemia | 0/10 (0%) | 2/165 (1.2%) | 1/147 (0.7%) | |||
| Bacterial Sepsis | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Bronchitis | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Bronchopulmonary Aspergillosis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Candida Infection | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Catheter Site Infection | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Cellulitis | 0/10 (0%) | 2/165 (1.2%) | 3/147 (2%) | |||
| Clostridial Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Clostridium Difficile Colitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Clostridium Difficile Infection | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Device Related Infection | 2/10 (20%) | 3/165 (1.8%) | 3/147 (2%) | |||
| Device Related Sepsis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Diverticulitis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Enterobacter Bacteraemia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Escherichia Bacteraemia | 0/10 (0%) | 0/165 (0%) | 3/147 (2%) | |||
| Escherichia Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Escherichia Sepsis | 2/10 (20%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Escherichia Urinary Tract Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Fungaemia | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Gastroenteritis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Gastroenteritis Rotavirus | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Gastroenteritis Viral | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Gastrointestinal Candidiasis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Hepatic Infection Fungal | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Infected Skin Ulcer | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Infection | 0/10 (0%) | 0/165 (0%) | 3/147 (2%) | |||
| Infectious Colitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Influenza | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Klebsiella Infection | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Liver Abscess | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Localised Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Lower Respiratory Tract Infection | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Lung Infection | 4/10 (40%) | 5/165 (3%) | 3/147 (2%) | |||
| Meningitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Moraxella Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Neutropenic Sepsis | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Oral Candidiasis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Parainfluenzae Virus Infection | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Parotitis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Periorbital Cellulitis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Pneumocystis Jirovecii Pneumonia | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Pneumonia | 0/10 (0%) | 23/165 (13.9%) | 24/147 (16.3%) | |||
| Pneumonia Fungal | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Pseudomembranous Colitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Pulmonary Mycosis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Pyelonephritis Acute | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Pyelonephritis Chronic | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Rash Pustular | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Respiratory Tract Infection | 0/10 (0%) | 0/165 (0%) | 4/147 (2.7%) | |||
| Rhinovirus Infection | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Sepsis | 2/10 (20%) | 6/165 (3.6%) | 14/147 (9.5%) | |||
| Septic Encephalopathy | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Septic Shock | 0/10 (0%) | 2/165 (1.2%) | 8/147 (5.4%) | |||
| Sinusitis Fungal | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Skin Infection | 1/10 (10%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Splenic Abscess | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Staphylococcal Infection | 1/10 (10%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Staphylococcal Sepsis | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Tooth Abscess | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Tooth Infection | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Urinary Tract Infection | 0/10 (0%) | 4/165 (2.4%) | 6/147 (4.1%) | |||
| Urosepsis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Viral Infection | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Vulval Cellulitis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Fall | 0/10 (0%) | 3/165 (1.8%) | 4/147 (2.7%) | |||
| Femoral Neck Fracture | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Femur Fracture | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Head Injury | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Hip Fracture | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Humerus Fracture | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Spinal Compression Fracture | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Transfusion Reaction | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Transfusion-Related Acute Lung Injury | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Traumatic Haematoma | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Investigations | ||||||
| Alanine Aminotransferase Increased | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Aspartate Aminotransferase Increased | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Blood Alkaline Phosphatase Increased | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Blood Lactate Dehydrogenase Increased | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| C-Reactive Protein Increased | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Gamma-Glutamyltransferase Increased | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Hyperglycaemia | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Hyperuricaemia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Hypokalaemia | 1/10 (10%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Hyponatraemia | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Hypovolaemia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Hypomagnesaemia | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthritis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Bursitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Chondrocalcinosis Pyrophosphate | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Muscular Weakness | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Pain in Extremity | 0/10 (0%) | 1/165 (0.6%) | 2/147 (1.4%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Acute Myeloid Leukaemia | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Bladder Neoplasm | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Central Nervous System Leukaemia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Chloroma | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Rectal Adenoma | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Transitional Cell Carcinoma | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Adenocarcinoma Gastric | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular Accident | 0/10 (0%) | 1/165 (0.6%) | 3/147 (2%) | |||
| Dizziness | 0/10 (0%) | 2/165 (1.2%) | 2/147 (1.4%) | |||
| Epilepsy | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Haemorrhage Intracranial | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Haemorrhagic Stroke | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Ischaemic Stroke | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Lethargy | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Paraesthesia | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Peripheral Sensory Neuropathy | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Presyncope | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Quadriparesis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Seizure | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Syncope | 0/10 (0%) | 1/165 (0.6%) | 4/147 (2.7%) | |||
| Transient Ischaemic Attack | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Vascular Encephalopathy | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Renal and urinary disorders | ||||||
| Acute Kidney Injury | 0/10 (0%) | 0/165 (0%) | 4/147 (2.7%) | |||
| Anuria | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Calculus Urinary | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Oliguria | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Renal Impairment | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Urinary Retention | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute Pulmonary Oedema | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Acute Respiratory Distress Syndrome | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Acute Respiratory Failure | 1/10 (10%) | 2/165 (1.2%) | 1/147 (0.7%) | |||
| Bronchopneumopathy | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Bronchospasm | 0/10 (0%) | 1/165 (0.6%) | 1/147 (0.7%) | |||
| Dyspnoea | 2/10 (20%) | 1/165 (0.6%) | 4/147 (2.7%) | |||
| Epistaxis | 0/10 (0%) | 2/165 (1.2%) | 2/147 (1.4%) | |||
| Hypoxia | 1/10 (10%) | 0/165 (0%) | 3/147 (2%) | |||
| Lung Infiltration | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Oropharyngeal Pain | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Pleural Effusion | 0/10 (0%) | 2/165 (1.2%) | 0/147 (0%) | |||
| Pneumonitis | 0/10 (0%) | 2/165 (1.2%) | 1/147 (0.7%) | |||
| Pulmonary Embolism | 0/10 (0%) | 1/165 (0.6%) | 2/147 (1.4%) | |||
| Pulmonary Hypertension | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Pulmonary Oedema | 0/10 (0%) | 1/165 (0.6%) | 2/147 (1.4%) | |||
| Respiratory Failure | 0/10 (0%) | 3/165 (1.8%) | 3/147 (2%) | |||
| Respiratory Tract Haemorrhage | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Pulmonary Haemorrhage | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Wheezing | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Hyperhidrosis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Rash Vesicular | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Vascular disorders | ||||||
| Deep Vein Thrombosis | 0/10 (0%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Hypertension | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Hypotension | 1/10 (10%) | 0/165 (0%) | 3/147 (2%) | |||
| Orthostatic Hypotension | 0/10 (0%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Phlebitis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Thrombosis | 0/10 (0%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Haemodynamic Instability | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Part A: Decitabine + JNJ-56022473 | Part B: Decitabine (Alone) | Part B: Decitabine + JNJ-56022473 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/10 (90%) | 157/165 (95.2%) | 146/147 (99.3%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 7/10 (70%) | 80/165 (48.5%) | 77/147 (52.4%) | |||
| Febrile Neutropenia | 4/10 (40%) | 22/165 (13.3%) | 25/147 (17%) | |||
| Leukocytosis | 0/10 (0%) | 9/165 (5.5%) | 1/147 (0.7%) | |||
| Leukopenia | 1/10 (10%) | 15/165 (9.1%) | 12/147 (8.2%) | |||
| Neutropenia | 1/10 (10%) | 61/165 (37%) | 64/147 (43.5%) | |||
| Thrombocytopenia | 3/10 (30%) | 86/165 (52.1%) | 81/147 (55.1%) | |||
| Splenomegaly | 1/10 (10%) | 2/165 (1.2%) | 2/147 (1.4%) | |||
| Cardiac disorders | ||||||
| Atrial Fibrillation | 0/10 (0%) | 8/165 (4.8%) | 13/147 (8.8%) | |||
| Tachycardia | 1/10 (10%) | 6/165 (3.6%) | 14/147 (9.5%) | |||
| Ear and labyrinth disorders | ||||||
| Tympanic Membrane Disorder | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Eye disorders | ||||||
| Uveitis | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal Pain | 1/10 (10%) | 12/165 (7.3%) | 19/147 (12.9%) | |||
| Abdominal Pain Upper | 2/10 (20%) | 6/165 (3.6%) | 9/147 (6.1%) | |||
| Anal Incontinence | 0/10 (0%) | 0/165 (0%) | 10/147 (6.8%) | |||
| Constipation | 3/10 (30%) | 51/165 (30.9%) | 47/147 (32%) | |||
| Diarrhoea | 4/10 (40%) | 41/165 (24.8%) | 50/147 (34%) | |||
| Dyspepsia | 1/10 (10%) | 5/165 (3%) | 10/147 (6.8%) | |||
| Gingival Bleeding | 0/10 (0%) | 10/165 (6.1%) | 2/147 (1.4%) | |||
| Haemorrhoids | 1/10 (10%) | 8/165 (4.8%) | 21/147 (14.3%) | |||
| Nausea | 5/10 (50%) | 33/165 (20%) | 36/147 (24.5%) | |||
| Stomatitis | 1/10 (10%) | 16/165 (9.7%) | 12/147 (8.2%) | |||
| Toothache | 0/10 (0%) | 9/165 (5.5%) | 4/147 (2.7%) | |||
| Vomiting | 5/10 (50%) | 19/165 (11.5%) | 26/147 (17.7%) | |||
| Abdominal Discomfort | 1/10 (10%) | 1/165 (0.6%) | 6/147 (4.1%) | |||
| Parotid Gland Enlargement | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Upper Gastrointestinal Haemorrhage | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| General disorders | ||||||
| Asthenia | 2/10 (20%) | 25/165 (15.2%) | 26/147 (17.7%) | |||
| Chills | 3/10 (30%) | 7/165 (4.2%) | 30/147 (20.4%) | |||
| Fatigue | 1/10 (10%) | 31/165 (18.8%) | 31/147 (21.1%) | |||
| Oedema Peripheral | 5/10 (50%) | 25/165 (15.2%) | 46/147 (31.3%) | |||
| Pain | 0/10 (0%) | 5/165 (3%) | 8/147 (5.4%) | |||
| Pyrexia | 6/10 (60%) | 46/165 (27.9%) | 51/147 (34.7%) | |||
| Gait Disturbance | 2/10 (20%) | 0/165 (0%) | 1/147 (0.7%) | |||
| General Physical Health Deterioration | 1/10 (10%) | 2/165 (1.2%) | 1/147 (0.7%) | |||
| Hepatobiliary disorders | ||||||
| Hyperbilirubinaemia | 2/10 (20%) | 7/165 (4.2%) | 3/147 (2%) | |||
| Infections and infestations | ||||||
| Oral Candidiasis | 2/10 (20%) | 6/165 (3.6%) | 9/147 (6.1%) | |||
| Oral Herpes | 3/10 (30%) | 9/165 (5.5%) | 11/147 (7.5%) | |||
| Pneumonia | 1/10 (10%) | 19/165 (11.5%) | 19/147 (12.9%) | |||
| Urinary Tract Infection | 0/10 (0%) | 13/165 (7.9%) | 13/147 (8.8%) | |||
| Bronchitis | 1/10 (10%) | 5/165 (3%) | 5/147 (3.4%) | |||
| Lung Infection | 1/10 (10%) | 4/165 (2.4%) | 2/147 (1.4%) | |||
| Lymph Gland Infection | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Oropharyngeal Candidiasis | 1/10 (10%) | 0/165 (0%) | 2/147 (1.4%) | |||
| Respiratory Tract Infection | 1/10 (10%) | 0/165 (0%) | 3/147 (2%) | |||
| Skin Infection | 1/10 (10%) | 3/165 (1.8%) | 2/147 (1.4%) | |||
| Systemic Mycosis | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Tooth Abscess | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Upper Respiratory Tract Infection | 1/10 (10%) | 6/165 (3.6%) | 2/147 (1.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/10 (0%) | 5/165 (3%) | 8/147 (5.4%) | |||
| Fall | 0/10 (0%) | 9/165 (5.5%) | 13/147 (8.8%) | |||
| Investigations | ||||||
| Alanine Aminotransferase Increased | 0/10 (0%) | 5/165 (3%) | 9/147 (6.1%) | |||
| Aspartate Aminotransferase Increased | 0/10 (0%) | 5/165 (3%) | 8/147 (5.4%) | |||
| Blood Creatinine Increased | 0/10 (0%) | 4/165 (2.4%) | 8/147 (5.4%) | |||
| Gamma-Glutamyltransferase Increased | 1/10 (10%) | 1/165 (0.6%) | 8/147 (5.4%) | |||
| Weight Decreased | 0/10 (0%) | 10/165 (6.1%) | 16/147 (10.9%) | |||
| Bacterial Test Positive | 1/10 (10%) | 0/165 (0%) | 1/147 (0.7%) | |||
| Hepatic Enzyme Increased | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| International Normalised Ratio Increased | 1/10 (10%) | 3/165 (1.8%) | 4/147 (2.7%) | |||
| Oxygen Saturation Decreased | 1/10 (10%) | 0/165 (0%) | 4/147 (2.7%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased Appetite | 4/10 (40%) | 31/165 (18.8%) | 25/147 (17%) | |||
| Hyperglycaemia | 0/10 (0%) | 4/165 (2.4%) | 17/147 (11.6%) | |||
| Hyperuricaemia | 0/10 (0%) | 8/165 (4.8%) | 9/147 (6.1%) | |||
| Hypoalbuminaemia | 0/10 (0%) | 5/165 (3%) | 13/147 (8.8%) | |||
| Hypocalcaemia | 1/10 (10%) | 9/165 (5.5%) | 14/147 (9.5%) | |||
| Hypokalaemia | 3/10 (30%) | 41/165 (24.8%) | 53/147 (36.1%) | |||
| Hypomagnesaemia | 2/10 (20%) | 12/165 (7.3%) | 20/147 (13.6%) | |||
| Hypophosphataemia | 1/10 (10%) | 5/165 (3%) | 9/147 (6.1%) | |||
| Fluid Overload | 1/10 (10%) | 4/165 (2.4%) | 6/147 (4.1%) | |||
| Fluid Retention | 1/10 (10%) | 4/165 (2.4%) | 1/147 (0.7%) | |||
| Hyperkalaemia | 1/10 (10%) | 4/165 (2.4%) | 5/147 (3.4%) | |||
| Hypoglycaemia | 1/10 (10%) | 2/165 (1.2%) | 2/147 (1.4%) | |||
| Hyponatraemia | 1/10 (10%) | 7/165 (4.2%) | 4/147 (2.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/10 (10%) | 15/165 (9.1%) | 12/147 (8.2%) | |||
| Back Pain | 0/10 (0%) | 18/165 (10.9%) | 19/147 (12.9%) | |||
| Pain in Extremity | 0/10 (0%) | 12/165 (7.3%) | 15/147 (10.2%) | |||
| Muscle Spasms | 1/10 (10%) | 4/165 (2.4%) | 2/147 (1.4%) | |||
| Muscular Weakness | 1/10 (10%) | 4/165 (2.4%) | 2/147 (1.4%) | |||
| Musculoskeletal Chest Pain | 1/10 (10%) | 4/165 (2.4%) | 1/147 (0.7%) | |||
| Myalgia | 1/10 (10%) | 3/165 (1.8%) | 4/147 (2.7%) | |||
| Nervous system disorders | ||||||
| Dizziness | 1/10 (10%) | 9/165 (5.5%) | 14/147 (9.5%) | |||
| Headache | 1/10 (10%) | 15/165 (9.1%) | 16/147 (10.9%) | |||
| Syncope | 2/10 (20%) | 5/165 (3%) | 6/147 (4.1%) | |||
| Somnolence | 1/10 (10%) | 2/165 (1.2%) | 2/147 (1.4%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 2/10 (20%) | 13/165 (7.9%) | 16/147 (10.9%) | |||
| Adjustment Disorder with Depressed Mood | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Agitation | 1/10 (10%) | 3/165 (1.8%) | 4/147 (2.7%) | |||
| Depressed Mood | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Hallucination | 1/10 (10%) | 2/165 (1.2%) | 1/147 (0.7%) | |||
| Nervousness | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Renal and urinary disorders | ||||||
| Acute Kidney Injury | 0/10 (0%) | 7/165 (4.2%) | 11/147 (7.5%) | |||
| Urinary Incontinence | 0/10 (0%) | 5/165 (3%) | 10/147 (6.8%) | |||
| Renal Impairment | 1/10 (10%) | 3/165 (1.8%) | 5/147 (3.4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/10 (10%) | 15/165 (9.1%) | 16/147 (10.9%) | |||
| Dyspnoea | 3/10 (30%) | 23/165 (13.9%) | 22/147 (15%) | |||
| Epistaxis | 1/10 (10%) | 13/165 (7.9%) | 20/147 (13.6%) | |||
| Hypoxia | 1/10 (10%) | 7/165 (4.2%) | 8/147 (5.4%) | |||
| Oropharyngeal Pain | 0/10 (0%) | 7/165 (4.2%) | 9/147 (6.1%) | |||
| Pleural Effusion | 1/10 (10%) | 10/165 (6.1%) | 4/147 (2.7%) | |||
| Bronchospasm | 3/10 (30%) | 1/165 (0.6%) | 6/147 (4.1%) | |||
| Pharyngeal Oedema | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Erythema | 0/10 (0%) | 4/165 (2.4%) | 9/147 (6.1%) | |||
| Petechiae | 1/10 (10%) | 10/165 (6.1%) | 11/147 (7.5%) | |||
| Pruritus | 1/10 (10%) | 12/165 (7.3%) | 11/147 (7.5%) | |||
| Rash | 1/10 (10%) | 11/165 (6.7%) | 13/147 (8.8%) | |||
| Hyperhidrosis | 1/10 (10%) | 2/165 (1.2%) | 7/147 (4.8%) | |||
| Dry Skin | 1/10 (10%) | 3/165 (1.8%) | 2/147 (1.4%) | |||
| Hidradenitis | 1/10 (10%) | 0/165 (0%) | 0/147 (0%) | |||
| Purpura | 1/10 (10%) | 1/165 (0.6%) | 0/147 (0%) | |||
| Skin Ulcer | 1/10 (10%) | 2/165 (1.2%) | 3/147 (2%) | |||
| Vascular disorders | ||||||
| Hypertension | 0/10 (0%) | 13/165 (7.9%) | 24/147 (16.3%) | |||
| Hypotension | 1/10 (10%) | 17/165 (10.3%) | 22/147 (15%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
| Name/Title | Senior Medical Director |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | 844-434-4210 |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02472145
Other Study ID Numbers:
- CR107273
- 56022473AML2002
- 2015-001611-12
First Posted:
Jun 15, 2015
Last Update Posted:
Mar 19, 2019
Last Verified:
Mar 1, 2019