Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

• Sponsor: City of Hope Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01876953
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 55.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of dasatinib when given together with cytarabine and idarubicin hydrochloride and to see how well they work in treating patients with acute myeloid leukemia that is likely to come back or spread. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and idarubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving dasatinib together with cytarabine and idarubicin hydrochloride may be a better treatment for acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia	Drug: cytarabine; Drug: idarubicin; Drug: dasatinib; Other: laboratory biomarker analysis	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Of the dose levels studied, to determine the maximum tolerated dose of dasatinib when given in combination with cytarabine and idarubicin for treatment of high risk acute myeloid leukemia (AML). (Phase I)

2. To determine the anti-tumor activity of dasatinib when given in combination with cytarabine and idarubicin, as assessed by complete remission rate (CR) and remission duration. (Phase II)

SECONDARY OBJECTIVES:

1. To document CR and survival outcomes (overall, event-free). (Phase I)

2. To estimate the survival probabilities (overall and event-free) and cumulative incidence of relapse/progression. (Phase II)

3. To describe and summarize all toxicities by organ and severity. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of dasatinib, followed by a phase II study.

Patients receive cytarabine intravenously (IV) continuously over 168 hours on days 1-7, dasatinib orally (PO) once daily (QD) on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 2 months for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of the Combination of Dasatinib With Chemotherapy for High Risk Acute Myeloid Leukemia (AML) Patients
• Actual Study Start Date: Sep 13, 2013
• Actual Primary Completion Date: Apr 25, 2018
• Actual Study Completion Date: Apr 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib 100mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.	Drug: cytarabine; Given IV; Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside ; Drug: idarubicin; Given IV; Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA ; Drug: dasatinib; Given PO; Other Names: BMS-354825 Sprycel ; Other: laboratory biomarker analysis; Correlative studies
Experimental: Dasatinib 140mg/day + Cytarabine 200mg/m2/day + Idarubicin 12mg/m2/day Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity.	Drug: cytarabine; Given IV; Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside ; Drug: idarubicin; Given IV; Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA ; Drug: dasatinib; Given PO; Other Names: BMS-354825 Sprycel ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose of Dasatinib (Phase I) [From the first dose of Dasatinib through the DLT observation period (Day +28)]

   Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

2. Complete Remission Rate (Phase II) [From the first cycle up to two years]

   Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.

Secondary Outcome Measures

1. Overall Survival (Phase II) [Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years]

   Overall survival was measured from the first dose of Dasatinib to death from any cause or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.

2. Event-free Survival (Phase II) [Time from start of study therapy until death, relapse/progression, receipt of anti-leukemia therapy, or last contact, whichever comes first, assessed up to two years.]

   Event-free survival was defined as time from the first dose of Dasatinib to relapse/progression, receipt of anti-leukemia therapy, death, or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients diagnosed with AML meeting one of the following criteria:

• Newly diagnosed, age 60 and older

• High risk cytogenetics and molecular abnormalities (National Comprehensive Cancer Network [NCCN] criteria)

• Relapsed or refractory to prior chemotherapy

• Secondary AML

• Any prior chemotherapy must have been completed >= 2 weeks prior to day 1 of study treatment and the participant must have recovered to eligibility levels from prior toxicity

• Only one prior regimen is allowed for relapsed AML patients; note one prior regimen is defined as follows:

• Induction chemotherapy followed by consolidation is considered one regimen

• Induction chemotherapy followed by re-induction in case of persistent disease followed by consolidation is considered one regimen

• Hydroxyurea is allowed prior to day 1 of study treatment to keep white blood cell (WBC) below 20 K

• Karnofsky performance status >= 60%

• Total bilirubin < 1.5 x institutional upper limit of normal

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal

• Creatinine < 1.5 x institutional upper limit or normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 x institutional upper limit of normal

• Ejection fraction (EF) >= 45%

• Ability to understand and sign a written informed consent document

• Patients should not be receiving any other investigational agents

Exclusion Criteria:

• Patients with clinically significant illness which would compromise participation in the study, including, but not limited to: active or uncontrolled infection, immune deficiencies or confirmed diagnosis of human immunodeficiency virus (HIV) infection, active hepatitis B, active hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmias; or psychiatric illness/social situations that would limit compliance with study requirements

• Patients with additional (other than AML) currently active primary malignancy other than curatively treated carcinoma in situ (CIS) of the cervix, or basal or squamous cell carcinoma of the skin; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy and disease free from prior malignancies for > 2 years

• Patients with active central nervous system (CNS) disease

• Patients with Chronic Myelogenous Leukemia (CML) in Myeloid blasts crisis

• Active infections, including opportunistic infections

• Women of childbearing potential (WOCBP) who have a positive serum pregnancy test within 14 days of the first administration of oral dasatinib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Medical Center	Duarte	California	United States	91010

Sponsors and Collaborators

• City of Hope Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ahmed Aribi, City of Hope Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 22, 2016

More Information

Publications

None provided.

• Responsible Party: City of Hope Medical Center
• ClinicalTrials.gov Identifier: NCT01876953
• Other Study ID Numbers: 12393; NCI-2013-01141
• First Posted: Jun 13, 2013
• Last Update Posted: Mar 31, 2022
• Last Verified: Mar 1, 2022

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Dasatinib; Idarubicin

Study Results

Participant Flow

Recruitment Details	Due to the funding issue, the study was stopped early before reaching the target accrual. However, all the enrolled patients had received the treatment drug per protocol.

Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day	Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	17	3
COMPLETED	17	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day	Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day	Total
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	17	3	20
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	63	63
Sex: Female, Male (Count of Participants)
Female	4 23.5%	1 33.3%	5 25%
Male	13 76.5%	2 66.7%	15 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 11.8%	0 0%	2 10%
Not Hispanic or Latino	15 88.2%	3 100%	18 90%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 17.6%	1 33.3%	4 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 5.9%	1 33.3%	2 10%
White	12 70.6%	1 33.3%	13 65%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5.9%	0 0%	1 5%
Region of Enrollment (Count of Participants)
United States	17 100%	3 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose of Dasatinib (Phase I)
Description	Maximum tolerated dose of dasatinib, determined according to incidence of dose limiting toxicity (DLT), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Time Frame	From the first dose of Dasatinib through the DLT observation period (Day +28)

Outcome Measure Data

Analysis Population Description

Six patients treated at 100 mg/m2 in Phase I are evaluable for dose limiting toxicity.

Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	6
Number [mg/m2]	100

2. Primary Outcome

Title	Complete Remission Rate (Phase II)
Description	Remission rates will be calculated as the percent of evaluable patients that have a confirmed CR, and exact 95% confidence intervals will be calculated for these estimates.
Time Frame	From the first cycle up to two years

Outcome Measure Data

Analysis Population Description

The study was terminated before the data were mature enough to estimate the CR rate. Therefore, the overall number of participants who were evaluable is zero.

Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day	Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	0	0

3. Secondary Outcome

Title	Overall Survival (Phase II)
Description	Overall survival was measured from the first dose of Dasatinib to death from any cause or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
Time Frame	Time from start of study therapy until death, or last contact, whichever comes first, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

The study was terminated before the data were mature enough to estimate the overall survival outcomes. Therefore, the overall number of participants who were evaluable is zero.

Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day	Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	0	0

4. Secondary Outcome

Title	Event-free Survival (Phase II)
Description	Event-free survival was defined as time from the first dose of Dasatinib to relapse/progression, receipt of anti-leukemia therapy, death, or last contact, whichever comes first. It was estimated using the product-limit method of Kaplan and Meier.
Time Frame	Time from start of study therapy until death, relapse/progression, receipt of anti-leukemia therapy, or last contact, whichever comes first, assessed up to two years.

Outcome Measure Data

Analysis Population Description

The study was terminated before the data were mature enough to estimate the even-free survival. Therefore, the overall number of participants who were evaluable is zero.

Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day	Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies
Measure Participants	0	0

Adverse Events

Time Frame	Adverse event and vital status data were captured from the initial treatment to off study, up to 2 years.
Adverse Event Reporting Description	From day 1 to day 30, the highest grade of non-hematologic toxicities were collected. For hematologic adverse events, from day 1 to day 30, collect every grade change for hematologic toxicities grade 3 and above. After the completion of treatment, report only the worst grade of each AE and only report AEs that are possibly, probably, or definitely related to Dasatinib.
Arm/Group Title	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day		Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
Arm/Group Description	Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies		Patients receive cytarabine IV continuously over 168 hours on days 1-7, dasatinib PO QD on days 1-7, and idarubicin hydrochloride IV on days 1-3. Patients with non-responsive disease on day 30 may receive a second course of therapy (re-induction therapy) within 1 week in the absence of unacceptable toxicity. cytarabine: Given IV idarubicin: Given IV dasatinib: Given PO laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day		Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/17 (64.7%)		3/3 (100%)
Serious Adverse Events
	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day		Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)		0/3 (0%)
General disorders
Death NOS	1/17 (5.9%)	1	0/3 (0%)	0
Multi-organ failure	1/17 (5.9%)	2	0/3 (0%)	0
Nervous system disorders
Intracranial hemorrhage	1/17 (5.9%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/17 (5.9%)	1	0/3 (0%)	0
Hypoxia	1/17 (5.9%)	1	0/3 (0%)	0
Respiratory failure	1/17 (5.9%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	Dasatinib 100mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day		Dasatinib 140mg/Day + Cytarabine 200mg/m2/Day + Idarubicin 12mg/m2/Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/17 (100%)		3/3 (100%)
Blood and lymphatic system disorders
10002272-Anemia	16/17 (94.1%)	83	3/3 (100%)	3
10016288-Febrile neutropenia	5/17 (29.4%)	12	0/3 (0%)	0
Markedly irregular multilobulated spleen with linear calcification	0/17 (0%)	0	1/3 (33.3%)	1
Splenomegaly	1/17 (5.9%)	1	0/3 (0%)	0
Cardiac disorders
10003658-Atrial fibrillation	1/17 (5.9%)	1	0/3 (0%)	0
10003662-Atrial flutter	1/17 (5.9%)	1	0/3 (0%)	0
10034474-Pericardial effusion	1/17 (5.9%)	2	2/3 (66.7%)	2
10040741-Sinus bradycardia	6/17 (35.3%)	12	0/3 (0%)	0
10040752-Sinus tachycardia	12/17 (70.6%)	34	1/3 (33.3%)	1
Atherosclerotic Vascular Disease	0/17 (0%)	0	1/3 (33.3%)	1
Left atrial enlargment	0/17 (0%)	0	1/3 (33.3%)	1
Nonspecific ST and T wave abnormality	1/17 (5.9%)	1	0/3 (0%)	0
cardiomegaly	1/17 (5.9%)	1	0/3 (0%)	0
cardiomyopathy	1/17 (5.9%)	1	0/3 (0%)	0
Ear and labyrinth disorders
10065837-External ear inflammation	1/17 (5.9%)	1	0/3 (0%)	0
Mastoiditis	1/17 (5.9%)	1	0/3 (0%)	0
right ear hearing loss	1/17 (5.9%)	3	0/3 (0%)	0
Endocrine disorders
syndrome of inappropriate antidiuretic hormone	1/17 (5.9%)	1	0/3 (0%)	0
Eye disorders
10005886-Blurred vision	1/17 (5.9%)	1	0/3 (0%)	0
10013774-Dry eye	2/17 (11.8%)	4	1/3 (33.3%)	1
10047848-Watering eyes	1/17 (5.9%)	1	0/3 (0%)	0
redness, jaundice, sclera/conjunctiva discoloration	0/17 (0%)	0	1/3 (33.3%)	1
scleral hemmorage	1/17 (5.9%)	1	0/3 (0%)	0
scleral hemorage	1/17 (5.9%)	1	0/3 (0%)	0
Gastrointestinal disorders
10000060-Abdominal distension	3/17 (17.6%)	4	0/3 (0%)	0
10000081-Abdominal pain	6/17 (35.3%)	6	2/3 (66.7%)	2
10003445-Ascites	1/17 (5.9%)	1	1/3 (33.3%)	1
10009887-Colitis	1/17 (5.9%)	1	0/3 (0%)	0
10010774-Constipation	7/17 (41.2%)	10	1/3 (33.3%)	1
10012727-Diarrhea	12/17 (70.6%)	24	3/3 (100%)	3
10013781-Dry mouth	5/17 (29.4%)	8	0/3 (0%)	0
10013946-Dyspepsia	3/17 (17.6%)	5	1/3 (33.3%)	1
10013950-Dysphagia	4/17 (23.5%)	5	0/3 (0%)	0
10015388-Esophageal pain	1/17 (5.9%)	1	0/3 (0%)	0
10016296-Fecal incontinence	1/17 (5.9%)	1	0/3 (0%)	0
10017999-Gastrointestinal pain	2/17 (11.8%)	2	0/3 (0%)	0
10018286-Gingival pain	1/17 (5.9%)	2	0/3 (0%)	0
10019611-Hemorrhoids	1/17 (5.9%)	1	2/3 (66.7%)	2
10028130-Mucositis oral	9/17 (52.9%)	21	2/3 (66.7%)	2
10028813-Nausea	13/17 (76.5%)	27	3/3 (100%)	3
10031009-Oral pain	3/17 (17.6%)	4	0/3 (0%)	0
10038072-Rectal pain	2/17 (11.8%)	2	0/3 (0%)	0
10044055-Toothache	1/17 (5.9%)	2	0/3 (0%)	0
10047700-Vomiting	9/17 (52.9%)	12	0/3 (0%)	0
10055356-Upper gastrointestinal hemorrhage	1/17 (5.9%)	1	0/3 (0%)	0
Anal fissure	0/17 (0%)	0	1/3 (33.3%)	1
Inguinal hernias	0/17 (0%)	0	1/3 (33.3%)	1
General disorders
10008531-Chills	4/17 (23.5%)	5	0/3 (0%)	0
10014222-Edema face	2/17 (11.8%)	3	0/3 (0%)	0
10016059-Facial pain	1/17 (5.9%)	1	0/3 (0%)	0
10016256-Fatigue	10/17 (58.8%)	26	3/3 (100%)	3
10016558-Fever	13/17 (76.5%)	36	2/3 (66.7%)	3
10017577-Gait disturbance	1/17 (5.9%)	1	0/3 (0%)	0
10022095-Injection site reaction	1/17 (5.9%)	1	0/3 (0%)	0
10025482-Malaise	1/17 (5.9%)	1	1/3 (33.3%)	1
10033371-Pain	4/17 (23.5%)	5	0/3 (0%)	0
10050068-Edema limbs	9/17 (52.9%)	17	3/3 (100%)	3
10051792-Infusion related reaction	1/17 (5.9%)	1	0/3 (0%)	0
10062466-Localized edema	1/17 (5.9%)	1	0/3 (0%)	0
10062501-Non-cardiac chest pain	3/17 (17.6%)	3	1/3 (33.3%)	1
generalized edema	1/17 (5.9%)	2	0/3 (0%)	0
Hepatobiliary disorders
biliary dyskinesia	1/17 (5.9%)	1	0/3 (0%)	0
Infections and infestations
10007810-Catheter related infection	2/17 (11.8%)	2	0/3 (0%)	0
10019799-Hepatitis viral	1/17 (5.9%)	1	0/3 (0%)	0
10040047-Sepsis	2/17 (11.8%)	2	0/3 (0%)	0
10040753-Sinusitis	0/17 (0%)	0	1/3 (33.3%)	1
10048038-Wound infection	1/17 (5.9%)	2	0/3 (0%)	0
10048762-Tooth infection	1/17 (5.9%)	2	0/3 (0%)	0
10061229-Lung infection	2/17 (11.8%)	3	1/3 (33.3%)	1
10062255-Soft tissue infection	1/17 (5.9%)	1	0/3 (0%)	0
10069138-Papulopustular rash	1/17 (5.9%)	1	0/3 (0%)	0
Candida Glabrata	0/17 (0%)	0	1/3 (33.3%)	1
Enterococci Faecium	0/17 (0%)	0	1/3 (33.3%)	1
Mastoiditis Grade 1 CT scan dated 10/9	1/17 (5.9%)	1	0/3 (0%)	0
Staphylococcus Coagulase Negative	0/17 (0%)	0	1/3 (33.3%)	1
Streptococcus viridans bacteremi	1/17 (5.9%)	1	0/3 (0%)	0
Upper lip herpetic lesion	0/17 (0%)	0	1/3 (33.3%)	1
Injury, poisoning and procedural complications
10006504-Bruising	2/17 (11.8%)	2	0/3 (0%)	0
10016173-Fall	1/17 (5.9%)	1	0/3 (0%)	0
Investigations
10000636-Activated partial thromboplastin time prolonged	0/17 (0%)	0	1/3 (33.3%)	1
10001551-Alanine aminotransferase increased	9/17 (52.9%)	12	2/3 (66.7%)	2
10001675-Alkaline phosphatase increased	6/17 (35.3%)	7	2/3 (66.7%)	2
10003481-Aspartate aminotransferase increased	9/17 (52.9%)	16	1/3 (33.3%)	1
10005364-Blood bilirubin increased	11/17 (64.7%)	34	3/3 (100%)	3
10007612-Cardiac troponin I increased	1/17 (5.9%)	1	0/3 (0%)	0
10011368-Creatinine increased	5/17 (29.4%)	5	0/3 (0%)	0
10022402-INR increased	0/17 (0%)	0	1/3 (33.3%)	1
10025256-Lymphocyte count decreased	15/17 (88.2%)	44	3/3 (100%)	3
10025258-Lymphocyte count increased	0/17 (0%)	0	1/3 (33.3%)	1
10029366-Neutrophil count decreased	12/17 (70.6%)	24	3/3 (100%)	3
10035528-Platelet count decreased	17/17 (100%)	119	3/3 (100%)	3
10047896-Weight gain	6/17 (35.3%)	13	2/3 (66.7%)	2
10047900-Weight loss	9/17 (52.9%)	17	1/3 (33.3%)	1
10049182-White blood cell decreased	16/17 (94.1%)	37	1/3 (33.3%)	1
10050528-Ejection fraction decreased	1/17 (5.9%)	1	0/3 (0%)	0
10056910-GGT increased	1/17 (5.9%)	1	0/3 (0%)	0
Metabolism and nutrition disorders
10000486-Acidosis	2/17 (11.8%)	4	0/3 (0%)	0
10001680-Alkalosis	2/17 (11.8%)	5	0/3 (0%)	0
10002646-Anorexia	10/17 (58.8%)	19	2/3 (66.7%)	2
10020639-Hyperglycemia	3/17 (17.6%)	4	0/3 (0%)	0
10020670-Hypermagnesemia	5/17 (29.4%)	5	1/3 (33.3%)	1
10020680-Hypernatremia	1/17 (5.9%)	3	0/3 (0%)	0
10020870-Hypertriglyceridemia	2/17 (11.8%)	2	0/3 (0%)	0
10020907-Hyperuricemia	2/17 (11.8%)	2	0/3 (0%)	0
10020943-Hypoalbuminemia	13/17 (76.5%)	49	3/3 (100%)	3
10020949-Hypocalcemia	12/17 (70.6%)	25	2/3 (66.7%)	2
10021005-Hypoglycemia	1/17 (5.9%)	1	0/3 (0%)	0
10021018-Hypokalemia	12/17 (70.6%)	42	3/3 (100%)	3
10021028-Hypomagnesemia	4/17 (23.5%)	5	1/3 (33.3%)	1
10021038-Hyponatremia	16/17 (94.1%)	37	2/3 (66.7%)	2
10021059-Hypophosphatemia	6/17 (35.3%)	9	0/3 (0%)	0
10029883-Obesity	1/17 (5.9%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
10003239-Arthralgia	1/17 (5.9%)	1	0/3 (0%)	0
10003246-Arthritis	1/17 (5.9%)	1	0/3 (0%)	0
10003988-Back pain	7/17 (41.2%)	13	3/3 (100%)	4
10006002-Bone pain	1/17 (5.9%)	1	0/3 (0%)	0
10016750-Flank pain	2/17 (11.8%)	2	0/3 (0%)	0
10028411-Myalgia	0/17 (0%)	0	1/3 (33.3%)	1
10028836-Neck pain	3/17 (17.6%)	5	0/3 (0%)	0
10033425-Pain in extremity	3/17 (17.6%)	4	3/3 (100%)	5
10048706-Joint range of motion decreased	1/17 (5.9%)	1	0/3 (0%)	0
10062572-Generalized muscle weakness	3/17 (17.6%)	5	0/3 (0%)	0
neck stiffness	1/17 (5.9%)	1	0/3 (0%)	0
Nervous system disorders
10012373-Depressed level of consciousness	1/17 (5.9%)	3	0/3 (0%)	0
10013911-Dysgeusia	1/17 (5.9%)	1	0/3 (0%)	0
10019211-Headache	9/17 (52.9%)	22	1/3 (33.3%)	1
10024264-Lethargy	2/17 (11.8%)	2	0/3 (0%)	0
10027175-Memory impairment	3/17 (17.6%)	3	0/3 (0%)	0
10034620-Peripheral sensory neuropathy	1/17 (5.9%)	1	0/3 (0%)	0
10039906-Seizure	2/17 (11.8%)	2	0/3 (0%)	0
10041349-Somnolence	3/17 (17.6%)	4	0/3 (0%)	0
10044565-Tremor	1/17 (5.9%)	1	0/3 (0%)	0
seizure-like disorder, altered mental status	1/17 (5.9%)	1	0/3 (0%)	0
Psychiatric disorders
10001497-Agitation	4/17 (23.5%)	6	1/3 (33.3%)	1
10002855-Anxiety	7/17 (41.2%)	12	0/3 (0%)	0
10010300-Confusion	3/17 (17.6%)	3	1/3 (33.3%)	1
10012378-Depression	2/17 (11.8%)	2	1/3 (33.3%)	1
10022437-Insomnia	5/17 (29.4%)	14	3/3 (100%)	3
10038743-Restlessness	4/17 (23.5%)	7	0/3 (0%)	0
Renal and urinary disorders
10019450-Hematuria	2/17 (11.8%)	2	0/3 (0%)	0
10037032-Proteinuria	3/17 (17.6%)	3	1/3 (33.3%)	1
10046539-Urinary frequency	1/17 (5.9%)	1	0/3 (0%)	0
10046543-Urinary incontinence	3/17 (17.6%)	3	0/3 (0%)	0
10069339-Acute kidney injury	2/17 (11.8%)	2	0/3 (0%)	0
Reproductive system and breast disorders
10013934-Dysmenorrhea	1/17 (5.9%)	1	0/3 (0%)	0
10018146-Genital edema	2/17 (11.8%)	7	0/3 (0%)	0
10039757-Scrotal pain	1/17 (5.9%)	1	0/3 (0%)	0
10046912-Vaginal hemorrhage	2/17 (11.8%)	3	0/3 (0%)	0
Thickened Endometrium	1/17 (5.9%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
10003598-Atelectasis	2/17 (11.8%)	2	1/3 (33.3%)	1
10011224-Cough	4/17 (23.5%)	5	3/3 (100%)	3
10013963-Dyspnea	5/17 (29.4%)	12	1/3 (33.3%)	1
10020201-Hoarseness	2/17 (11.8%)	2	0/3 (0%)	0
10021143-Hypoxia	4/17 (23.5%)	5	0/3 (0%)	0
10028735-Nasal congestion	1/17 (5.9%)	1	1/3 (33.3%)	1
10035598-Pleural effusion	4/17 (23.5%)	4	3/3 (100%)	3
10035623-Pleuritic pain	2/17 (11.8%)	2	0/3 (0%)	0
10035742-Pneumonitis	3/17 (17.6%)	3	0/3 (0%)	0
10036402-Postnasal drip	1/17 (5.9%)	1	0/3 (0%)	0
10036790-Productive cough	1/17 (5.9%)	1	1/3 (33.3%)	1
10037375-Pulmonary edema	1/17 (5.9%)	1	0/3 (0%)	0
10037400-Pulmonary hypertension	1/17 (5.9%)	1	0/3 (0%)	0
10040975-Sleep apnea	1/17 (5.9%)	1	0/3 (0%)	0
10041367-Sore throat	5/17 (29.4%)	6	0/3 (0%)	0
10047924-Wheezing	3/17 (17.6%)	3	0/3 (0%)	0
Bilateral lower lobe interstitial changes possible infiltrates.	1/17 (5.9%)	1	0/3 (0%)	0
Emphysema	0/17 (0%)	0	1/3 (33.3%)	1
LLL infiltrate	0/17 (0%)	0	1/3 (33.3%)	1
Peribronchial infiltrate	1/17 (5.9%)	1	0/3 (0%)	0
Pneumonia	0/17 (0%)	0	1/3 (33.3%)	1
Rales	0/17 (0%)	0	1/3 (33.3%)	1
Right bundle branch block	1/17 (5.9%)	1	0/3 (0%)	0
chest infiltrate	0/17 (0%)	0	1/3 (33.3%)	1
pneumonia	1/17 (5.9%)	1	0/3 (0%)	0
respiratory acidosis	1/17 (5.9%)	1	0/3 (0%)	0
tachypnea	1/17 (5.9%)	1	0/3 (0%)	0
vascular congestion	1/17 (5.9%)	1	0/3 (0%)	0
Skin and subcutaneous tissue disorders
10001760-Alopecia	0/17 (0%)	0	2/3 (66.7%)	2
10013786-Dry skin	3/17 (17.6%)	3	0/3 (0%)	0
10037087-Pruritus	6/17 (35.3%)	6	0/3 (0%)	0
10037847-Rash acneiform	1/17 (5.9%)	1	0/3 (0%)	0
10037868-Rash maculo-papular	11/17 (64.7%)	25	3/3 (100%)	3
10040865-Skin hyperpigmentation	1/17 (5.9%)	1	0/3 (0%)	0
10040947-Skin ulceration	2/17 (11.8%)	2	0/3 (0%)	0
10051837-Skin induration	1/17 (5.9%)	1	0/3 (0%)	0
10054524-Palmar-plantar erythrodysesthesia syndrome	1/17 (5.9%)	3	1/3 (33.3%)	1
10054541-Periorbital edema	3/17 (17.6%)	4	1/3 (33.3%)	1
Ecchymosis	0/17 (0%)	0	1/3 (33.3%)	1
blisters	1/17 (5.9%)	1	0/3 (0%)	0
desquamation in both hands	1/17 (5.9%)	1	0/3 (0%)	0
nasal lesions	1/17 (5.9%)	1	0/3 (0%)	0
petechial rash	2/17 (11.8%)	3	0/3 (0%)	0
Vascular disorders
10007196-Capillary leak syndrome	1/17 (5.9%)	1	0/3 (0%)	0
10016825-Flushing	3/17 (17.6%)	3	0/3 (0%)	0
10019428-Hematoma	1/17 (5.9%)	1	0/3 (0%)	0
10020772-Hypertension	16/17 (94.1%)	100	3/3 (100%)	4
10021097-Hypotension	4/17 (23.5%)	10	0/3 (0%)	0
10043565-Thromboembolic event	1/17 (5.9%)	1	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.