Efficacy and Safety of Decitabine as Epigenetic Priming With Induction Chemotherapy in Pediatric Acute Myelogenous Leukemia (AML) Subjects
Study Details
Study Description
Brief Summary
The purpose of this study is to provide data on the activity of a standard daunorubicin, cytarabine, and etoposide (ADE) induction plus epigenetic priming with decitabine as assessed by standard measures of complete remission (CR), leukemia free survival (LFS) and overall survival (OS), as well as, on minimal residual disease (MRD). It will also provide necessary data on the safety and Pharmacokinetics (PK) of decitabine in pediatric patients that is currently unavailable.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A
|
Drug: Decitabine
5 day priming with decitabine followed by Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide).
|
| Experimental: Arm B
|
Drug: Decitabine
Induction Chemotherapy of ADE (daunorubicin, cytarabine, etoposide) only
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Morphologic Complete Remission (CR) [Day 50]
Disease response measurements were based on bone marrow evaluations (biopsies, aspirates, or both) performed by local pathology laboratories and assessed by study investigators. A designation of CR required that the participant achieve a morphologic leukemia-free state and have an absolute neutrophil count (ANC) greater than 1000 per microliter (/mcL) and a platelet count greater than 100,000/mcL.
Secondary Outcome Measures
- DNA Methylation [Baseline up to completion of induction therapy (Day 15)]
Bone marrow samples were obtained at baseline and completion of induction therapy. DNA was extracted, and global DNA methylation was evaluated using the Infinium® Human Methylation450® BeadChip Array according to the manufacturer's protocol (Illumina, San Diego, California). Paired differential methylation analysis of end-induction marrows to participant matched screening marrows was performed to identify differentially methylated cytosines followed by guanine residue (CpG) loci (DML). A paired Wilcoxon rank test was conducted to compare end-induction marrows with diagnostic marrows within each arm to identify loci considered statistically significant and differentially methylated. Three different behaviors were defined: 'hypermethylation' (increased intensity in the tumor), 'hypomethylation' (decreased intensity in the tumor) and 'no change' (no substantial differences of intensity).
- Leukemia-free Survival (LFS) [Baseline to recurrence of Leukemia or Death (up to 2 years 5 months)]
LFS was defined as time from CR until the recurrence of leukemia (greater than or equal to [>=] 5% bone marrow blasts, reappearance of peripheral blasts or the appearance of new dysplastic changes, or death, whichever occurred first). For participants who did not achieve a CR, LFS is set to zero days. For participants with CR who do not have leukemic recurrence or death, data for LFS was censored on the date of the last follow-up bone marrow or hematology examination, whichever is later. LFS was analyzed using Kaplan-Meier method.
- Overall Survival (OS) [Baseline to Date of Death (up to 2 years 5 months)]
OS was defined as the time from the date of the first dose of study treatment to the date of death from any cause. OS was analyzed using Kaplan-Meier method.
- Percentage of Participants With Minimal Residual Disease (MRD) at Baseline and Day 50 [Baseline and Day 50]
After induction chemotherapy, based on bone marrow biopsies. No formal statistical analyses of MRD were performed for this study.
- Time to CR [Randomization to Day 50]
Disease response measurements were based on bone marrow evaluations (biopsies, aspirates, or both) performed by local pathology laboratories an assessed by study investigators. CR: requires that the participant achieved a morphologic leukemia-free state and had an ANC >1000/mcL and platelets >100,000/mcL. Hemoglobin concentration or hematocrit had no bearing on remission status, although the participant had to be independent of transfusions. Kaplan-Meier curves were used to describe time to CR.
- Time to Neutrophil Recovery [Baseline up to Day 50]
Blood sampling was used to determine recovery, and is defined as less than or equal to 1000 per cubic millimeter (/mm^3) for absolute neutrophil count (ANC). Summarized using Kaplan-Meier product limit estimators.
- Time to Platelet Recovery [Baseline up to Day 38]
Blood sampling was used to determine recovery and is defined as less than or equal to 100,000/mm^3 for platelet count. Summarized using Kaplan-Meier product limit estimators.
Eligibility Criteria
Criteria
Inclusion Criteria
-
Males and females, age 1 to 16 years, inclusive
-
Females of childbearing potential must have a negative serum beta human chorionic gonadotropin ( B-hCG) at Visit 1 (Screening) and a negative urine pregnancy test prior to starting study drugs (Visit 2). Female subjects of childbearing potential must agree to be abstinent or to use a highly effective method of contraception (eg, condom
- spermicide, condom + diaphragm with spermicide, intrauterine devise (IUD), or have a vasectomised partner) for at least one menstrual cycle prior to starting study drug(s) and throughout the Randomization Phase or 30 days after the last dose of study drug. Those females using hormonal contraceptives must also be using an additional approved method of contraception (as described previously)
-
Sexually mature male patients who are not abstinent or have not undergone a successful vasectomy, who are partners of women of childbearing potential must use, or their partners must use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, IUD) starting for at least one menstrual cycle prior to starting study drug(s) and throughout the Randomization Phase and for 30 days (longer if appropriate) after the last dose of study drug. Those with partners using hormonal contraceptives must also be using an additional approved method of contraception (as described previously)
-
Diagnosis of acute myelogenous leukemia ( AML) (bone marrow or peripheral blood blasts greater than or equal to 20%)
-
Adequate cardiac function as defined by an echocardiogram or multiple gated acquisition (MUGA) scan demonstrating an ejection fraction greater than 50%
-
Are willing and able to comply with all aspects of the protocol
-
Provide written informed consent from subject's guardian or legally authorized representative and child assent (if applicable).
Exclusion Criteria
-
Females who are pregnant (positive B-hCG test) or lactating
-
History of chronic myelogenous leukemia (CML) [t(9;22)]
-
Acute promyelocytic leukemia (M3 subtype in French-American-British [FAB] classification)
-
Known central nervous system (CNS) leukemia
-
AML associated with congenital syndromes such as Down syndrome, Fanconi anemia, Bloom syndrome, Kostmann syndrome, or Diamond-Blackfan anemia
-
White blood cell (WBC) count greater than 100,000/mm3
-
Serum creatinine greater than 2.5 mg/dL
-
Alanine aminotransferase (ALT) greater than 5 x upper limit of normal (ULN) and/or total bilirubin greater than 3 x ULN
-
Prior chemotherapy (other than hydroxyurea) or radiation therapy for AML
-
Known to be human immunodeficiency virus (HIV) positive
-
Any history of or concomitant medical condition that, in the opinion of the Investigator, would compromise the subject's ability to safely complete the study
-
The Investigator believes the subject to be medically unfit to receive the study drug or unsuitable for any other reason
-
Subject with hypersensitivity to decitabine, daunorubicin, cytarabine, or etoposide
-
Has participated in a drug trial in the last 4 weeks.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Phoenix | Arizona | United States | ||
| 2 | Madera | California | United States | ||
| 3 | Aurora | Colorado | United States | ||
| 4 | Miami | Florida | United States | ||
| 5 | Atlanta | Georgia | United States | ||
| 6 | Baltimore | Maryland | United States | ||
| 7 | Boston | Massachusetts | United States | ||
| 8 | Worcester | Massachusetts | United States | ||
| 9 | Rochester | Minnesota | United States | ||
| 10 | New Hyde Park | New York | United States | ||
| 11 | New York | New York | United States | ||
| 12 | Charlotte | North Carolina | United States | ||
| 13 | Columbus | Ohio | United States | ||
| 14 | Portland | Oregon | United States | ||
| 15 | Dallas | Texas | United States | ||
| 16 | Salt Lake City | Utah | United States | ||
| 17 | Seattle | Washington | United States | ||
| 18 | New Lambton Heights | New South Wales | Australia | ||
| 19 | Westmead | New South Wales | Australia | ||
| 20 | Parkville | Victoria | Australia | ||
| 21 | Subiaco | Western Australia | Australia | ||
| 22 | Calgary | Alberta | Canada |
Sponsors and Collaborators
- Eisai Inc.
Investigators
- Study Director: Eisai Medical Services, Eisai Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E7373-G000-202
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 11 investigative sites in Australia, Canada and the United States from 3 March 2011 to 19 July 2013. |
|---|---|
| Pre-assignment Detail | A total of 98 participants were screened, of which 25 were enrolled and treated in the study. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 milligram per square meter (mg/m^2) infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Period Title: Overall Study | ||
| STARTED | 11 | 14 |
| COMPLETED | 10 | 14 |
| NOT COMPLETED | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only | Total |
|---|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. | Total of all reporting groups |
| Overall Participants | 11 | 14 | 25 |
| Age, Customized (participants) [Number] | |||
| 1 to less than (<) 2 years |
0
0%
|
1
7.1%
|
1
4%
|
| 2 to 11 years |
7
63.6%
|
8
57.1%
|
15
60%
|
| 12 to 16 years |
4
36.4%
|
5
35.7%
|
9
36%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
7
63.6%
|
6
42.9%
|
13
52%
|
| Male |
4
36.4%
|
8
57.1%
|
12
48%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
9.1%
|
5
35.7%
|
6
24%
|
| Not Hispanic or Latino |
10
90.9%
|
9
64.3%
|
19
76%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
1
9.1%
|
0
0%
|
1
4%
|
| Asian |
0
0%
|
1
7.1%
|
1
4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
9.1%
|
0
0%
|
1
4%
|
| White |
8
72.7%
|
12
85.7%
|
20
80%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
9.1%
|
1
7.1%
|
2
8%
|
Outcome Measures
| Title | Percentage of Participants With Morphologic Complete Remission (CR) |
|---|---|
| Description | Disease response measurements were based on bone marrow evaluations (biopsies, aspirates, or both) performed by local pathology laboratories and assessed by study investigators. A designation of CR required that the participant achieve a morphologic leukemia-free state and have an absolute neutrophil count (ANC) greater than 1000 per microliter (/mcL) and a platelet count greater than 100,000/mcL. |
| Time Frame | Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 11 | 14 |
| Number (95% Confidence Interval) [percentage of participants] |
27.3
248.2%
|
50.0
357.1%
|
| Title | DNA Methylation |
|---|---|
| Description | Bone marrow samples were obtained at baseline and completion of induction therapy. DNA was extracted, and global DNA methylation was evaluated using the Infinium® Human Methylation450® BeadChip Array according to the manufacturer's protocol (Illumina, San Diego, California). Paired differential methylation analysis of end-induction marrows to participant matched screening marrows was performed to identify differentially methylated cytosines followed by guanine residue (CpG) loci (DML). A paired Wilcoxon rank test was conducted to compare end-induction marrows with diagnostic marrows within each arm to identify loci considered statistically significant and differentially methylated. Three different behaviors were defined: 'hypermethylation' (increased intensity in the tumor), 'hypomethylation' (decreased intensity in the tumor) and 'no change' (no substantial differences of intensity). |
| Time Frame | Baseline up to completion of induction therapy (Day 15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 11 | 14 |
| Measure Loci | 6990 | 1090 |
| Hypomethylated DML |
4134
|
785
|
| Hypermethylated DML |
2856
|
305
|
| Title | Leukemia-free Survival (LFS) |
|---|---|
| Description | LFS was defined as time from CR until the recurrence of leukemia (greater than or equal to [>=] 5% bone marrow blasts, reappearance of peripheral blasts or the appearance of new dysplastic changes, or death, whichever occurred first). For participants who did not achieve a CR, LFS is set to zero days. For participants with CR who do not have leukemic recurrence or death, data for LFS was censored on the date of the last follow-up bone marrow or hematology examination, whichever is later. LFS was analyzed using Kaplan-Meier method. |
| Time Frame | Baseline to recurrence of Leukemia or Death (up to 2 years 5 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The per protocol set included all participants who sufficiently complied with protocol. Here "overall number of participants analyzed" are participants who achieved morphologic CR and were available for this outcome measure assessment at given time period. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 3 | 7 |
| Median (Full Range) [days] |
NA
|
NA
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from the date of the first dose of study treatment to the date of death from any cause. OS was analyzed using Kaplan-Meier method. |
| Time Frame | Baseline to Date of Death (up to 2 years 5 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The per protocol set included all participants who sufficiently complied with protocol. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 11 | 14 |
| Median (Full Range) [months] |
NA
|
NA
|
| Title | Percentage of Participants With Minimal Residual Disease (MRD) at Baseline and Day 50 |
|---|---|
| Description | After induction chemotherapy, based on bone marrow biopsies. No formal statistical analyses of MRD were performed for this study. |
| Time Frame | Baseline and Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time points. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 8 | 9 |
| At Baseline |
75
681.8%
|
NA
NaN
|
| At Day 50 |
25
227.3%
|
11
78.6%
|
| Title | Time to CR |
|---|---|
| Description | Disease response measurements were based on bone marrow evaluations (biopsies, aspirates, or both) performed by local pathology laboratories an assessed by study investigators. CR: requires that the participant achieved a morphologic leukemia-free state and had an ANC >1000/mcL and platelets >100,000/mcL. Hemoglobin concentration or hematocrit had no bearing on remission status, although the participant had to be independent of transfusions. Kaplan-Meier curves were used to describe time to CR. |
| Time Frame | Randomization to Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. Here "overall number of participants analyzed" are participants who achieved morphologic CR and were available for this outcome measure assessment at given time period. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 3 | 7 |
| Median (95% Confidence Interval) [days] |
43.0
|
37.0
|
| Title | Time to Neutrophil Recovery |
|---|---|
| Description | Blood sampling was used to determine recovery, and is defined as less than or equal to 1000 per cubic millimeter (/mm^3) for absolute neutrophil count (ANC). Summarized using Kaplan-Meier product limit estimators. |
| Time Frame | Baseline up to Day 50 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response. Here "overall number of participants analyzed" are participants who were available for this outcome measure assessment at given time period. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 9 | 10 |
| Median (95% Confidence Interval) [days] |
26.0
|
18.0
|
| Title | Time to Platelet Recovery |
|---|---|
| Description | Blood sampling was used to determine recovery and is defined as less than or equal to 100,000/mm^3 for platelet count. Summarized using Kaplan-Meier product limit estimators. |
| Time Frame | Baseline up to Day 38 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all participants who received at least one dose of study treatment and who had at least one postdose efficacy measurement for response All participants in FAS had platelet recovery. |
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only |
|---|---|---|
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. |
| Measure Participants | 11 | 14 |
| Median (95% Confidence Interval) [days] |
22.0
|
14.5
|
Adverse Events
| Time Frame | For each participant, from the time the participant signed the informed consent form until the AE resolved, or for 30 days after the participant's last study visit, whichever came first (approximately up to 2 years and 5 months) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only | ||
| Arm/Group Description | Participants received decitabine 20 mg/m^2 infusion, intravenously, daily from Days 1 to 5, followed by induction chemotherapy of daunorubicin, cytarabine, etoposide for 10 days. | Participants received induction chemotherapy of daunorubicin, cytarabine, etoposide only for 10 days. | ||
All Cause Mortality |
||||
| Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/11 (27.3%) | 3/14 (21.4%) | ||
Serious Adverse Events |
||||
| Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/11 (18.2%) | 1/14 (7.1%) | ||
| Gastrointestinal disorders | ||||
| Lower gastrointestinal hemorrhage | 1/11 (9.1%) | 0/14 (0%) | ||
| Infections and infestations | ||||
| Appendicitis | 1/11 (9.1%) | 0/14 (0%) | ||
| Sepsis | 0/11 (0%) | 1/14 (7.1%) | ||
| Injury, poisoning and procedural complications | ||||
| Large intestine perforation | 1/11 (9.1%) | 0/14 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Treatment A: Decitabine + Induction Chemotherapy | Treatment B: Induction Chemotherapy Only | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/11 (72.7%) | 9/14 (64.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 6/11 (54.5%) | 4/14 (28.6%) | ||
| Coagulopathy | 1/11 (9.1%) | 0/14 (0%) | ||
| Febrile neutropenia | 1/11 (9.1%) | 4/14 (28.6%) | ||
| Lymphopenia | 0/11 (0%) | 1/14 (7.1%) | ||
| Neutropenia | 3/11 (27.3%) | 1/14 (7.1%) | ||
| Thrombocytopenia | 4/11 (36.4%) | 2/14 (14.3%) | ||
| Cardiac disorders | ||||
| Bradycardia | 1/11 (9.1%) | 2/14 (14.3%) | ||
| Sinus arrhythmia | 1/11 (9.1%) | 0/14 (0%) | ||
| Sinus bradycardia | 2/11 (18.2%) | 0/14 (0%) | ||
| Sinus tachycardia | 2/11 (18.2%) | 0/14 (0%) | ||
| Tachycardia | 3/11 (27.3%) | 1/14 (7.1%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 0/11 (0%) | 3/14 (21.4%) | ||
| Tinnitus | 1/11 (9.1%) | 0/14 (0%) | ||
| Eye disorders | ||||
| Dry eye | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Vision blurred | 1/11 (9.1%) | 0/14 (0%) | ||
| Visual impairment | 1/11 (9.1%) | 0/14 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/11 (27.3%) | 6/14 (42.9%) | ||
| Abdominal pain upper | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Abdominal tenderness | 1/11 (9.1%) | 0/14 (0%) | ||
| Anorectal discomfort | 2/11 (18.2%) | 0/14 (0%) | ||
| Ascites | 1/11 (9.1%) | 0/14 (0%) | ||
| Caecitis | 2/11 (18.2%) | 0/14 (0%) | ||
| Colitis | 1/11 (9.1%) | 0/14 (0%) | ||
| Constipation | 5/11 (45.5%) | 2/14 (14.3%) | ||
| Diarrhoea | 6/11 (54.5%) | 4/14 (28.6%) | ||
| Dyspepsia | 1/11 (9.1%) | 0/14 (0%) | ||
| Epigastric discomfort | 0/11 (0%) | 1/14 (7.1%) | ||
| Faeces discoloured | 1/11 (9.1%) | 0/14 (0%) | ||
| Flatulence | 1/11 (9.1%) | 0/14 (0%) | ||
| Gastric fistula | 1/11 (9.1%) | 0/14 (0%) | ||
| Gingival bleeding | 1/11 (9.1%) | 0/14 (0%) | ||
| Gingivitis | 1/11 (9.1%) | 0/14 (0%) | ||
| Lip disorder | 1/11 (9.1%) | 0/14 (0%) | ||
| Lip dry | 2/11 (18.2%) | 0/14 (0%) | ||
| Lip pain | 1/11 (9.1%) | 0/14 (0%) | ||
| Lip ulceration | 0/11 (0%) | 1/14 (7.1%) | ||
| Lower gastrointestinal haemorrhage | 2/11 (18.2%) | 0/14 (0%) | ||
| Mouth ulceration | 1/11 (9.1%) | 0/14 (0%) | ||
| Nausea | 4/11 (36.4%) | 5/14 (35.7%) | ||
| Oral pain | 4/11 (36.4%) | 1/14 (7.1%) | ||
| Proctalgia | 1/11 (9.1%) | 0/14 (0%) | ||
| Proctitis | 2/11 (18.2%) | 0/14 (0%) | ||
| Rectal haemorrhage | 1/11 (9.1%) | 0/14 (0%) | ||
| Stomatitis | 2/11 (18.2%) | 2/14 (14.3%) | ||
| Swollen tongue | 1/11 (9.1%) | 0/14 (0%) | ||
| Toothache | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Vomiting | 5/11 (45.5%) | 3/14 (21.4%) | ||
| General disorders | ||||
| Asthenia | 2/11 (18.2%) | 0/14 (0%) | ||
| Catheter site discharge | 2/11 (18.2%) | 0/14 (0%) | ||
| Catheter site erosion | 1/11 (9.1%) | 0/14 (0%) | ||
| Catheter site erythema | 5/11 (45.5%) | 2/14 (14.3%) | ||
| Catheter site haematoma | 0/11 (0%) | 1/14 (7.1%) | ||
| Catheter site haemorrhage | 2/11 (18.2%) | 0/14 (0%) | ||
| Catheter site oedema | 1/11 (9.1%) | 0/14 (0%) | ||
| Catheter site pain | 3/11 (27.3%) | 3/14 (21.4%) | ||
| Catheter site pruritus | 3/11 (27.3%) | 0/14 (0%) | ||
| Catheter site related reaction | 1/11 (9.1%) | 0/14 (0%) | ||
| Chest discomfort | 1/11 (9.1%) | 0/14 (0%) | ||
| Chest pain | 0/11 (0%) | 1/14 (7.1%) | ||
| Chills | 1/11 (9.1%) | 0/14 (0%) | ||
| Fatigue | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Generalised oedema | 1/11 (9.1%) | 0/14 (0%) | ||
| Hypothermia | 2/11 (18.2%) | 0/14 (0%) | ||
| Localised oedema | 1/11 (9.1%) | 0/14 (0%) | ||
| Medical device complication | 1/11 (9.1%) | 0/14 (0%) | ||
| Mucosal inflammation | 0/11 (0%) | 1/14 (7.1%) | ||
| Nodule | 1/11 (9.1%) | 0/14 (0%) | ||
| Oedema peripheral | 1/11 (9.1%) | 0/14 (0%) | ||
| Pain | 2/11 (18.2%) | 0/14 (0%) | ||
| Puncture site pain | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Pyrexia | 3/11 (27.3%) | 2/14 (14.3%) | ||
| Swelling | 0/11 (0%) | 1/14 (7.1%) | ||
| Thrombosis in device | 2/11 (18.2%) | 0/14 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholangitis | 1/11 (9.1%) | 0/14 (0%) | ||
| Hepatomegaly | 1/11 (9.1%) | 0/14 (0%) | ||
| Immune system disorders | ||||
| Drug hypersensitivity | 1/11 (9.1%) | 0/14 (0%) | ||
| Graft versus host disease | 1/11 (9.1%) | 0/14 (0%) | ||
| Hypersensitivity | 1/11 (9.1%) | 0/14 (0%) | ||
| Infections and infestations | ||||
| Bacterial infection | 0/11 (0%) | 1/14 (7.1%) | ||
| Herpes simplex | 0/11 (0%) | 1/14 (7.1%) | ||
| Lower respiratory tract infection | 1/11 (9.1%) | 0/14 (0%) | ||
| Lung infection | 1/11 (9.1%) | 0/14 (0%) | ||
| Pneumonia | 1/11 (9.1%) | 0/14 (0%) | ||
| Vulvovaginal candidiasis | 0/11 (0%) | 1/14 (7.1%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 2/11 (18.2%) | 0/14 (0%) | ||
| Laceration | 1/11 (9.1%) | 0/14 (0%) | ||
| Post lumbar puncture syndrome | 1/11 (9.1%) | 0/14 (0%) | ||
| Post procedural haematoma | 1/11 (9.1%) | 0/14 (0%) | ||
| Procedural nausea | 1/11 (9.1%) | 0/14 (0%) | ||
| Procedural pain | 1/11 (9.1%) | 0/14 (0%) | ||
| Procedural vomiting | 1/11 (9.1%) | 0/14 (0%) | ||
| Tongue injury | 1/11 (9.1%) | 0/14 (0%) | ||
| Transfusion reaction | 1/11 (9.1%) | 0/14 (0%) | ||
| Vascular access complication | 1/11 (9.1%) | 0/14 (0%) | ||
| Wound | 1/11 (9.1%) | 0/14 (0%) | ||
| Investigations | ||||
| Blood creatinine increased | 1/11 (9.1%) | 0/14 (0%) | ||
| Breath sounds abnormal | 1/11 (9.1%) | 0/14 (0%) | ||
| Cardiac murmur | 1/11 (9.1%) | 0/14 (0%) | ||
| Granulocyte count decreased | 0/11 (0%) | 1/14 (7.1%) | ||
| Heart rate irregular | 2/11 (18.2%) | 0/14 (0%) | ||
| Lymphocyte count decreased | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Neutrophil count decreased | 0/11 (0%) | 3/14 (21.4%) | ||
| Platelet count decreased | 1/11 (9.1%) | 3/14 (21.4%) | ||
| Weight decreased | 3/11 (27.3%) | 4/14 (28.6%) | ||
| Weight increased | 1/11 (9.1%) | 1/14 (7.1%) | ||
| White blood cell count decreased | 6/11 (54.5%) | 5/14 (35.7%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 6/11 (54.5%) | 3/14 (21.4%) | ||
| Dehydration | 1/11 (9.1%) | 0/14 (0%) | ||
| Hyperglycaemia | 1/11 (9.1%) | 0/14 (0%) | ||
| Hyperkalaemia | 1/11 (9.1%) | 0/14 (0%) | ||
| Hyperphosphataemia | 1/11 (9.1%) | 0/14 (0%) | ||
| Hypoalbuminaemia | 1/11 (9.1%) | 0/14 (0%) | ||
| Hypocalcaemia | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Hypokalaemia | 3/11 (27.3%) | 1/14 (7.1%) | ||
| Hypophosphataemia | 2/11 (18.2%) | 0/14 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/11 (18.2%) | 1/14 (7.1%) | ||
| Back pain | 0/11 (0%) | 1/14 (7.1%) | ||
| Joint swelling | 1/11 (9.1%) | 0/14 (0%) | ||
| Musculoskeletal chest pain | 1/11 (9.1%) | 0/14 (0%) | ||
| Musculoskeletal pain | 0/11 (0%) | 1/14 (7.1%) | ||
| Myalgia | 0/11 (0%) | 1/14 (7.1%) | ||
| Neck pain | 0/11 (0%) | 2/14 (14.3%) | ||
| Pain in extremity | 2/11 (18.2%) | 0/14 (0%) | ||
| Soft tissue mass | 0/11 (0%) | 1/14 (7.1%) | ||
| Nervous system disorders | ||||
| Cognitive disorder | 2/11 (18.2%) | 0/14 (0%) | ||
| Dizziness | 2/11 (18.2%) | 1/14 (7.1%) | ||
| Dizziness postural | 1/11 (9.1%) | 0/14 (0%) | ||
| Headache | 3/11 (27.3%) | 4/14 (28.6%) | ||
| Lethargy | 1/11 (9.1%) | 0/14 (0%) | ||
| Migraine | 1/11 (9.1%) | 0/14 (0%) | ||
| Paraesthesia | 0/11 (0%) | 1/14 (7.1%) | ||
| Presyncope | 1/11 (9.1%) | 0/14 (0%) | ||
| Somnolence | 1/11 (9.1%) | 0/14 (0%) | ||
| Psychiatric disorders | ||||
| Agitation | 1/11 (9.1%) | 0/14 (0%) | ||
| Anxiety | 0/11 (0%) | 2/14 (14.3%) | ||
| Hallucination | 0/11 (0%) | 1/14 (7.1%) | ||
| Insomnia | 1/11 (9.1%) | 0/14 (0%) | ||
| Mood altered | 1/11 (9.1%) | 0/14 (0%) | ||
| Restlessness | 1/11 (9.1%) | 0/14 (0%) | ||
| Social avoidant behaviour | 1/11 (9.1%) | 0/14 (0%) | ||
| Renal and urinary disorders | ||||
| Bladder disorder | 1/11 (9.1%) | 0/14 (0%) | ||
| Cystitis noninfective | 1/11 (9.1%) | 0/14 (0%) | ||
| Dysuria | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Urinary incontinence | 1/11 (9.1%) | 0/14 (0%) | ||
| Urinary retention | 0/11 (0%) | 1/14 (7.1%) | ||
| Reproductive system and breast disorders | ||||
| Menorrhagia | 0/11 (0%) | 1/14 (7.1%) | ||
| Menstrual disorder | 1/11 (9.1%) | 0/14 (0%) | ||
| Menstruation irregular | 1/11 (9.1%) | 0/14 (0%) | ||
| Penis disorder | 1/11 (9.1%) | 0/14 (0%) | ||
| Vaginal discharge | 1/11 (9.1%) | 0/14 (0%) | ||
| Vaginal haemorrhage | 2/11 (18.2%) | 0/14 (0%) | ||
| Vulvovaginal pain | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Bradypnoea | 1/11 (9.1%) | 0/14 (0%) | ||
| Cough | 2/11 (18.2%) | 1/14 (7.1%) | ||
| Dyspnoea | 2/11 (18.2%) | 0/14 (0%) | ||
| Epistaxis | 1/11 (9.1%) | 3/14 (21.4%) | ||
| Hiccups | 1/11 (9.1%) | 0/14 (0%) | ||
| Hypoxia | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Nasal congestion | 1/11 (9.1%) | 0/14 (0%) | ||
| Oropharyngeal pain | 1/11 (9.1%) | 2/14 (14.3%) | ||
| Pleural effusion | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Pulmonary oedema | 1/11 (9.1%) | 0/14 (0%) | ||
| Rhinalgia | 0/11 (0%) | 1/14 (7.1%) | ||
| Rhinorrhoea | 1/11 (9.1%) | 0/14 (0%) | ||
| Tachypnoea | 3/11 (27.3%) | 0/14 (0%) | ||
| Tonsillar hypertrophy | 1/11 (9.1%) | 0/14 (0%) | ||
| Upper-airway cough syndrome | 0/11 (0%) | 1/14 (7.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 4/11 (36.4%) | 3/14 (21.4%) | ||
| Dermatitis acneiform | 0/11 (0%) | 1/14 (7.1%) | ||
| Drug eruption | 1/11 (9.1%) | 0/14 (0%) | ||
| Dry skin | 2/11 (18.2%) | 0/14 (0%) | ||
| Hyperhidrosis | 1/11 (9.1%) | 0/14 (0%) | ||
| Ingrowing nail | 0/11 (0%) | 1/14 (7.1%) | ||
| Nail disorder | 1/11 (9.1%) | 0/14 (0%) | ||
| Night sweats | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Papule | 1/11 (9.1%) | 0/14 (0%) | ||
| Petechiae | 3/11 (27.3%) | 1/14 (7.1%) | ||
| Photosensitivity reaction | 1/11 (9.1%) | 0/14 (0%) | ||
| Pruritus | 3/11 (27.3%) | 3/14 (21.4%) | ||
| Rash | 3/11 (27.3%) | 2/14 (14.3%) | ||
| Rash erythematous | 0/11 (0%) | 1/14 (7.1%) | ||
| Rash generalised | 1/11 (9.1%) | 1/14 (7.1%) | ||
| Rash maculo-papular | 1/11 (9.1%) | 2/14 (14.3%) | ||
| Rash pruritic | 1/11 (9.1%) | 0/14 (0%) | ||
| Skin disorder | 1/11 (9.1%) | 0/14 (0%) | ||
| Skin hyperpigmentation | 1/11 (9.1%) | 0/14 (0%) | ||
| Skin irritation | 0/11 (0%) | 1/14 (7.1%) | ||
| Urticaria | 0/11 (0%) | 2/14 (14.3%) | ||
| Vascular disorders | ||||
| Haematoma | 1/11 (9.1%) | 0/14 (0%) | ||
| Hot flush | 1/11 (9.1%) | 0/14 (0%) | ||
| Hypertension | 3/11 (27.3%) | 0/14 (0%) | ||
| Hypotension | 5/11 (45.5%) | 1/14 (7.1%) | ||
| Orthostatic hypotension | 1/11 (9.1%) | 0/14 (0%) | ||
| Pallor | 1/11 (9.1%) | 0/14 (0%) | ||
| Phlebitis | 0/11 (0%) | 1/14 (7.1%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Eisai Medical Services |
|---|---|
| Organization | Eisai, Inc. |
| Phone | 1-888-422-4743 |
| esi_medinfo@eisai.com |
- E7373-G000-202