301: Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia

• Sponsor: Jazz Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01696084
• Collaborator: The Leukemia and Lymphoma Society (Other)
• Enrollment: 309
• Locations: 43
• Arms: 2
• Actual Duration (Months): 36.6
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To confirm the efficacy of CPX-351 compared to 7+3 as first line therapy in elderly patients (60-75 yrs) with high risk (secondary) Acute Myeloid Leukemia. The primary efficacy endpoint will be overall survival.

Condition or Disease	Intervention/Treatment	Phase
High Risk Acute Myeloid Leukemia	Drug: CPX-351; Drug: 7+3 (cytarabine and daunorubicin)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 309 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III, Multicenter, Randomized, Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients 60-75 Years of Age With Untreated High Risk (Secondary) AML
• Actual Study Start Date: Dec 13, 2012
• Actual Primary Completion Date: Dec 31, 2015
• Actual Study Completion Date: Dec 31, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (CPX-351) Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Drug: CPX-351; First induction: 100 units/m2 by 90-minute IV infusion on Days 1, 3, 5. Second induction: 100 units/m2 by 90-minute IV infusion on Days 1 and 3. Consolidation therapy: 65 units/m2 by 90-minute IV infusion on Days 1 and 3.
Active Comparator: Arm B (7+3) Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.	Drug: 7+3 (cytarabine and daunorubicin); First induction: 7+3 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 7 by continuous infusion, and daunorubicin at a dose of 60 mg/m2/day on Days 1, 2, and 3. Second induction: 5+2 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 5 by continuous infusion and daunorubicin at a dose of 60 mg/m2/day on Days 1 and 2. Consolidation therapy: 5+2 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 5 by continuous infusion, and daunorubicin at a dose of 60 mg/m2/day on Days 1 and 2.; Other Names: cytarabine and daunorubicin

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From the date of randomization to death from any cause]

   Overall survival was measured from the date of randomization to death from any cause, subjects not known to have died by the last follow-up were censored on the date they were last known to be alive.

Secondary Outcome Measures

1. Proportion of Subjects With a Response [Post Induction]

   Complete Remission (CR)

2. Event-free Survival [From the date of randomization to the date that persistent disease was documented or the date of relapse after CR or death, whichever came first]

   All randomized subjects were assessed for event-free survival (EFS). EFS was defined as the time from study randomization to the date of induction treatment failure (persistent disease), relapse from CR or CRi or death from any cause, whichever came first. Subjects alive and not known to have any of these events were censored on thee date they were last examined on study.

3. Remission Duration [From the date of achievement of a remission until the date of relapse or death from any cause]

   Only subjects achieving CR or CRi were assessed for remission duration.

4. Rate of Achieving Morphologic Leukemia-free State [Day 14]

   All randomized subjects with at least 1 evaluable postrandomization bone marrow assessment performed on or after Day 14 after the last induction were assessed for MLFS.

5. Proportion of Subjects Receiving a Stem Cell Transplant [Post Induction]

   The number and percentage of subjects transferred for HSCT after induction treatment was recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to understand and voluntarily give informed consent

• Age 60-75 years at the time of diagnosis of AML

• Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow)

• Confirmation of:

• Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease

• AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS

• AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL

• De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Able to adhere to the study visit schedule and other protocol requirements

• Laboratory values fulfilling the following:

• Serum creatinine < 2.0 mg/dL

• Serum total bilirubin < 2.0 mg/dL, patients with Gilbert's Syndrome should contact the medical monitor

• Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN Note: If elevated liver enzymes, above the ULN, are related to disease; contact medical monitor to discuss.

• Cardiac ejection fraction ≥ 50% by echocardiography or MUGA

• Patients with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible.

Exclusion Criteria:

• Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.

• Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization.

• Clinical evidence of active CNS leukemia

• Patients with active (uncontrolled, metastatic) second malignancies are excluded.

• Prior treatment intended for induction therapy of AML; only hydroxyurea is permitted for control of blood counts. For example, a patient with MDS that changes HMA dose and schedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabine alone (>1g/m2/day) or cytarabine plus an anthracycline as well as prior HSCT are also excluded.

• Administration of any therapy for MDS (conventional or investigational) must be completed by 2 weeks prior to of the first dose of study drug; in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment. Toxicities associated with prior MDS therapy must have recovered to grade 1 or less prior to start of treatment.

• Any major surgery or radiation therapy within four weeks.

• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).

• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent

• Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging)

• Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs.

• Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values)

• Hypersensitivity to cytarabine, daunorubicin or liposomal products

• History of Wilson's disease or other copper-metabolism disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	UCLA	Los Angeles	California	United States	90095
3	University of CA San Diego	San Diego	California	United States	92037-0706
4	Stanford University	Stanford	California	United States	94305
5	Yale University	New Haven	Connecticut	United States	06510
6	University of Florida	Gainesville	Florida	United States	32611
7	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
8	Northside Hospital	Atlanta	Georgia	United States	30342
9	Northwestern University	Chicago	Illinois	United States	60208
10	Rush University Medical Center	Chicago	Illinois	United States	60612
11	University of Chicago	Chicago	Illinois	United States	60637
12	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
13	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
14	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
15	University of Michigan	Ann Arbor	Michigan	United States	48109
16	University of Minnesota	Minneapolis	Minnesota	United States	55455
17	University of Missouri	Columbia	Missouri	United States	65211
18	Washington University	Saint Louis	Missouri	United States	63110
19	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
21	Montefiore Medical Center	Bronx	New York	United States	10467
22	North Shore LIJ Health System	Long Island City	New York	United States
23	Columbia University	New York	New York	United States	10032
24	Cornell U, Weill Medical College	New York	New York	United States	10065
25	New York Medical College	Valhalla	New York	United States	10595
26	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-1651
27	Duke University Medical Center	Durham	North Carolina	United States	27710
28	Wake Forest University Health Services	Winston-Salem	North Carolina	United States	27157
29	Providence Portland Medical Center	Portland	Oregon	United States	97213
30	Oregon Health and Science University	Portland	Oregon	United States	97239
31	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
32	UPMC	Pittsburgh	Pennsylvania	United States	15219
33	Medical University of South Carolina	Charleston	South Carolina	United States	29425
34	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
35	Vanderbilt University	Nashville	Tennessee	United States	37232
36	Baylor Research Insitute	Dallas	Texas	United States	75246
37	M.D. Anderson Cancer Center	Houston	Texas	United States	770303
38	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
39	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
40	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2C8
41	British Columbia Cancer Center	Vancouver	British Columbia	Canada	V5Z 1M9
42	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G2M9
43	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada

Sponsors and Collaborators

• Jazz Pharmaceuticals
• The Leukemia and Lymphoma Society

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jazz Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01696084
• Other Study ID Numbers: CLTR0310-301
• First Posted: Sep 28, 2012
• Last Update Posted: Aug 10, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by Jazz Pharmaceuticals: AML; Acute Myeloid Leukemia; high risk AML; secondary AML; AML in elderly
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Cytarabine; Daunorubicin

Study Results

Participant Flow

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Period Title: Overall Study
STARTED	153	156
COMPLETED	22	10
NOT COMPLETED	131	146

Baseline Characteristics

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)	Total
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.	Total of all reporting groups
Overall Participants	153	156	309
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.8 (4.19)	67.7 (4.1)	67.7 (4.14)
Sex: Female, Male (Count of Participants)
Female	59 38.6%	60 38.5%	119 38.5%
Male	94 61.4%	96 61.5%	190 61.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.7%	0 0%	1 0.3%
Asian	6 3.9%	2 1.3%	8 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 4.6%	6 3.8%	13 4.2%
White	128 83.7%	139 89.1%	267 86.4%
More than one race	0 0%	1 0.6%	1 0.3%
Unknown or Not Reported	11 7.2%	8 5.1%	19 6.1%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival was measured from the date of randomization to death from any cause, subjects not known to have died by the last follow-up were censored on the date they were last known to be alive.
Time Frame	From the date of randomization to death from any cause

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants randomized in the study.

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Measure Participants	153	156
Median (95% Confidence Interval) [months]	9.56	5.95

2. Secondary Outcome

Title	Proportion of Subjects With a Response
Description	Complete Remission (CR)
Time Frame	Post Induction

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants randomized in the study.

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Measure Participants	153	156
Count of Participants [Participants]	57 37.3%	40 25.6%

3. Secondary Outcome

Title	Event-free Survival
Description	All randomized subjects were assessed for event-free survival (EFS). EFS was defined as the time from study randomization to the date of induction treatment failure (persistent disease), relapse from CR or CRi or death from any cause, whichever came first. Subjects alive and not known to have any of these events were censored on thee date they were last examined on study.
Time Frame	From the date of randomization to the date that persistent disease was documented or the date of relapse after CR or death, whichever came first

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants randomized in the study.

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Measure Participants	153	156
Median (95% Confidence Interval) [months]	2.53	1.31

4. Secondary Outcome

Title	Remission Duration
Description	Only subjects achieving CR or CRi were assessed for remission duration.
Time Frame	From the date of achievement of a remission until the date of relapse or death from any cause

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants randomized in the study.

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Measure Participants	153	156
Median (95% Confidence Interval) [months]	6.93	6.11

5. Secondary Outcome

Title	Rate of Achieving Morphologic Leukemia-free State
Description	All randomized subjects with at least 1 evaluable postrandomization bone marrow assessment performed on or after Day 14 after the last induction were assessed for MLFS.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants randomized in the study.

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Measure Participants	126	119
Count of Participants [Participants]	87 56.9%	66 42.3%

6. Secondary Outcome

Title	Proportion of Subjects Receiving a Stem Cell Transplant
Description	The number and percentage of subjects transferred for HSCT after induction treatment was recorded.
Time Frame	Post Induction

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: All participants randomized in the study.

Arm/Group Title	Arm A (CPX-351)	Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
Measure Participants	153	156
Count of Participants [Participants]	52 34%	39 25%

Adverse Events

Time Frame	Adverse events (AE) recorded from the start of the infusion on Day 1 to the last day of the treatment period. SAE recorded from the start of the infusion on Day 1 to 30 days after completion of the treatment period.
Adverse Event Reporting Description	Safety Population: All randomized participants who received at least one dose of study treatment.
Arm/Group Title	Arm A (CPX-351)		Arm B (7+3)
Arm/Group Description	Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with CPX-351. The number of inductions and consolidations a subject received depended on response.		Subjects are eligible to receive up to 2 inductions and up to 2 consolidations with cytarabine and daunorubicin given as a 7 + 3, or 5 days of continuous infusion of cytarabine and 2 days of daunorubicin (5+2, second induction, consolidation courses) therapy. The number of inductions and consolidations a subject received depended on response.
All Cause Mortality
	Arm A (CPX-351)		Arm B (7+3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/153 (0.7%)		0/151 (0%)
Serious Adverse Events
	Arm A (CPX-351)		Arm B (7+3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/153 (58.8%)		65/151 (43%)
Blood and lymphatic system disorders
Febrile Neutropenia	12/153 (7.8%)		8/151 (5.3%)
Anaemia	2/153 (1.3%)		1/151 (0.7%)
Thrombocytopenia	1/153 (0.7%)		1/151 (0.7%)
Leukocytosis	0/153 (0%)		1/151 (0.7%)
Neutropenia	1/153 (0.7%)		0/151 (0%)
Pancytopenia	1/153 (0.7%)		0/151 (0%)
Cardiac disorders
Atrial Fibrillation	2/153 (1.3%)		2/151 (1.3%)
Cardiac Failure	2/153 (1.3%)		2/151 (1.3%)
Left Ventricular Dysfunction	0/153 (0%)		4/151 (2.6%)
Myocardial Infarction	3/153 (2%)		0/151 (0%)
Cardiac Arrest	1/153 (0.7%)		1/151 (0.7%)
Cardiac Failure Congestive	1/153 (0.7%)		1/151 (0.7%)
Cardiomyopathy	1/153 (0.7%)		1/151 (0.7%)
Acute Myocardial Infarction	0/153 (0%)		1/151 (0.7%)
Cardio-Respiratory Arrest	0/153 (0%)		1/151 (0.7%)
Cardiotoxicity	0/153 (0%)		1/151 (0.7%)
Cytotoxic Cardiomyopathy	0/153 (0%)		1/151 (0.7%)
Mitral Valve Incompetence	1/153 (0.7%)		0/151 (0%)
Pericarditis	1/153 (0.7%)		0/151 (0%)
Supraventricular Tachycardia	0/153 (0%)		1/151 (0.7%)
Tachycardia	1/153 (0.7%)		0/151 (0%)
Ventricular Tachycardia	0/153 (0%)		1/151 (0.7%)
Endocrine disorders
Euthyroid Sick Syndrome	1/153 (0.7%)		0/151 (0%)
Hypothyroidism	1/153 (0.7%)		0/151 (0%)
Eye disorders
Conjunctival Haemorrhage	0/153 (0%)		1/151 (0.7%)
Gastrointestinal disorders
Colitis	0/153 (0%)		2/151 (1.3%)
Small Intestinal Disorders	1/153 (0.7%)		1/151 (0.7%)
Chron's Disease	1/153 (0.7%)		0/151 (0%)
Dysphagia	1/153 (0.7%)		0/151 (0%)
Gastric Haemorrhage	1/153 (0.7%)		0/151 (0%)
Gingival Bleeding	1/153 (0.7%)		0/151 (0%)
Lower Gastrointestinal Haemorrhage	1/153 (0.7%)		0/151 (0%)
Rectal Haemorrhage	0/153 (0%)		1/151 (0.7%)
General disorders
Disease Progression	6/153 (3.9%)		6/151 (4%)
Multi-Organ Failure	2/153 (1.3%)		4/151 (2.6%)
Chest Pain	1/153 (0.7%)		1/151 (0.7%)
Asthenia	0/153 (0%)		1/151 (0.7%)
Chest Discomfort	1/153 (0.7%)		0/151 (0%)
Death	1/153 (0.7%)		0/151 (0%)
Non-Cardiac Chest Pain	1/153 (0.7%)		0/151 (0%)
Pyrexia	0/153 (0%)		1/151 (0.7%)
Hepatobiliary disorders
Cholecystitis Acute	2/153 (1.3%)		0/151 (0%)
Bile Duct Stone	1/153 (0.7%)		0/151 (0%)
Immune system disorders
Alloimmunisation	1/153 (0.7%)		0/151 (0%)
Infections and infestations
Sepsis	12/153 (7.8%)		5/151 (3.3%)
Pneumonia	10/153 (6.5%)		6/151 (4%)
Bacteraemia	4/153 (2.6%)		0/151 (0%)
Cellulitis	3/153 (2%)		1/151 (0.7%)
Septic Shock	2/153 (1.3%)		2/151 (1.3%)
Enterococcal Bacteraemia	1/153 (0.7%)		2/151 (1.3%)
Staphylococcal Bacteraemia	1/153 (0.7%)		2/151 (1.3%)
Lung Infection	0/153 (0%)		2/151 (1.3%)
Pneumonia Bacterial	1/153 (0.7%)		1/151 (0.7%)
Bacteroides Bacteraemia	1/153 (0.7%)		0/151 (0%)
Bronchopulmonary Aspergillosis	1/153 (0.7%)		0/151 (0%)
Central Nervous System Infection	0/153 (0%)		1/151 (0.7%)
Diverticulitis	1/153 (0.7%)		0/151 (0%)
Enterobacter Bacteraemia	1/153 (0.7%)		0/151 (0%)
Escherichia Bacteraemia	0/153 (0%)		1/151 (0.7%)
Escherichia Sepsis	0/153 (0%)		1/151 (0.7%)
Klebsiella Bacteraemia	0/153 (0%)		1/151 (0.7%)
Klebsiella Sepsis	0/153 (0%)		1/151 (0.7%)
Mycotic Aneurysm	1/153 (0.7%)		0/151 (0%)
Neutropenic Infection	1/153 (0.7%)		0/151 (0%)
Pneumonia Fungal	0/153 (0%)		1/151 (0.7%)
Pneumonia Pseudomonas Aeruginosa	0/153 (0%)		1/151 (0.7%)
Pseudomonal Bacteraemia	1/153 (0.7%)		0/151 (0%)
Sinusitis	1/153 (0.7%)		0/151 (0%)
Sinusitis Fungal	1/153 (0.7%)		0/151 (0%)
Skin Infection	1/153 (0.7%)		0/151 (0%)
Staphylococcal Infection	0/153 (0%)		1/151 (0.7%)
Streptococcal Sepsis	1/153 (0.7%)		0/151 (0%)
Urinary Tract Infection	1/153 (0.7%)		0/151 (0%)
Injury, poisoning and procedural complications
Subdural Haemorrhage	0/153 (0%)		2/151 (1.3%)
Transfusion Reaction	2/153 (1.3%)		0/151 (0%)
Brain Herniation	0/153 (0%)		1/151 (0.7%)
Fall	1/153 (0.7%)		0/151 (0%)
Subdural Haematoma	0/153 (0%)		1/151 (0.7%)
Transfusion-Related Acute Lung Injury	1/153 (0.7%)		0/151 (0%)
Investigations
Ejection Fraction Decreased	9/153 (5.9%)		9/151 (6%)
Enterococcus Test Positive	1/153 (0.7%)		0/151 (0%)
Fungal Test Positive	1/153 (0.7%)		0/151 (0%)
Hepatic Enzyme Increased	1/153 (0.7%)		0/151 (0%)
Klebsiella Test Positive	0/153 (0%)		1/151 (0.7%)
Pseudomonas Test Positive	1/153 (0.7%)		0/151 (0%)
Staphylococcus Test Positive	1/153 (0.7%)		0/151 (0%)
Stenotrophomonas Test Positive	1/153 (0.7%)		0/151 (0%)
Streptococcus Test Positive	1/153 (0.7%)		0/151 (0%)
Metabolism and nutrition disorders
Dehydration	1/153 (0.7%)		0/151 (0%)
Lactic Acidosis	1/153 (0.7%)		0/151 (0%)
Tumor Lysis Syndrome	0/153 (0%)		1/151 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/153 (0.7%)		0/151 (0%)
Back Pain	1/153 (0.7%)		0/151 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia	1/153 (0.7%)		1/151 (0.7%)
Leukaemia	0/153 (0%)		2/151 (1.3%)
Acute Myeloid Leukaemia Recurrent	1/153 (0.7%)		0/151 (0%)
Myelodysplastic Syndrome	1/153 (0.7%)		0/151 (0%)
Renal Cell Carcinoma	1/153 (0.7%)		0/151 (0%)
Nervous system disorders
Syncope	4/153 (2.6%)		0/151 (0%)
Central Nervous System Haemorrhage	3/153 (2%)		0/151 (0%)
Cerebral Haemorrhage	1/153 (0.7%)		2/151 (1.3%)
Haemorrhage Intracranial	1/153 (0.7%)		1/151 (0.7%)
Carotid Artery Stenosis	1/153 (0.7%)		0/151 (0%)
Cerebral Infarction	1/153 (0.7%)		0/151 (0%)
Convulsion	1/153 (0.7%)		0/151 (0%)
Headache	1/153 (0.7%)		0/151 (0%)
Presyncope	1/153 (0.7%)		0/151 (0%)
Radiculopathy	1/153 (0.7%)		0/151 (0%)
Psychiatric disorders
Confusional State	2/153 (1.3%)		0/151 (0%)
Delirium	1/153 (0.7%)		0/151 (0%)
Mental Status Changes	1/153 (0.7%)		0/151 (0%)
Renal and urinary disorders
Renal Failure Acute	2/153 (1.3%)		2/151 (1.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	11/153 (7.2%)		8/151 (5.3%)
Acute Respiratory Failure	6/153 (3.9%)		3/151 (2%)
Hypoxia	3/153 (2%)		3/151 (2%)
Pulmonary Oedema	1/153 (0.7%)		3/151 (2%)
Respiratory Distress	0/153 (0%)		2/151 (1.3%)
Acute Respiratory Distress Syndrome	1/153 (0.7%)		0/151 (0%)
Dyspnoea	1/153 (0.7%)		0/151 (0%)
Epistaxis	1/153 (0.7%)		0/151 (0%)
Hypercapnia	0/153 (0%)		1/151 (0.7%)
Pleural Effusion	0/153 (0%)		1/151 (0.7%)
Pneumonia Aspiration	1/153 (0.7%)		0/151 (0%)
Pneumothorax	1/153 (0.7%)		0/151 (0%)
Pulmonary Embolism	0/153 (0%)		1/151 (0.7%)
Pulmonary Haemorrhage	0/153 (0%)		1/151 (0.7%)
Vascular disorders
Deep Vein Thrombosis	1/153 (0.7%)		0/151 (0%)
Hypotension	1/153 (0.7%)		0/151 (0%)
Other (Not Including Serious) Adverse Events
	Arm A (CPX-351)		Arm B (7+3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	152/153 (99.3%)		151/151 (100%)
Blood and lymphatic system disorders
Febrile Neutropenia	104/153 (68%)		105/151 (69.5%)
Cardiac disorders
Atrial Fibrillation	8/153 (5.2%)		15/151 (9.9%)
Tachycardia	22/153 (14.4%)		17/151 (11.3%)
Eye disorders
Conjunctival Haemorrhage	8/153 (5.2%)		6/151 (4%)
Vision Blurred	10/153 (6.5%)		2/151 (1.3%)
Gastrointestinal disorders
Diarrhoea	70/153 (45.8%)		103/151 (68.2%)
Nausea	75/153 (49%)		83/151 (55%)
Constipation	65/153 (42.5%)		60/151 (39.7%)
Vomiting	39/153 (25.5%)		33/151 (21.9%)
Abdominal Pain	33/153 (21.6%)		30/151 (19.9%)
Abdominal Distension	18/153 (11.8%)		17/151 (11.3%)
Haemorrhoids	18/153 (11.8%)		12/151 (7.9%)
Stomatitis	14/153 (9.2%)		16/151 (10.6%)
Mouth Haemorrhage	16/153 (10.5%)		8/151 (5.3%)
Dry Mouth	11/153 (7.2%)		12/151 (7.9%)
Dyspepsia	14/153 (9.2%)		9/151 (6%)
Dysphagia	9/153 (5.9%)		10/151 (6.6%)
Gingival Bleeding	12/153 (7.8%)		7/151 (4.6%)
Oral Pain	5/153 (3.3%)		10/151 (6.6%)
Abdominal Pain Upper	9/153 (5.9%)		4/151 (2.6%)
Gastrooesophageal Reflux Disease	4/153 (2.6%)		9/151 (6%)
Mouth Ulceration	9/153 (5.9%)		2/151 (1.3%)
General disorders
Oedema Peripheral	62/153 (40.5%)		76/151 (50.3%)
Fatigue	53/153 (34.6%)		53/151 (35.1%)
Chills	41/153 (26.8%)		41/151 (27.2%)
Mucosal Inflammation	28/153 (18.3%)		31/151 (20.5%)
Pyrexia	33/153 (21.6%)		25/151 (16.6%)
Asthenia	14/153 (9.2%)		14/151 (9.3%)
Oedema	13/153 (8.5%)		14/151 (9.3%)
Chest Pain	11/153 (7.2%)		13/151 (8.6%)
Catheter Site Erythema	9/153 (5.9%)		7/151 (4.6%)
Catheter Site Pain	11/153 (7.2%)		4/151 (2.6%)
Chest Discomfort	8/153 (5.2%)		6/151 (4%)
Infections and infestations
Pneumonia	28/153 (18.3%)		26/151 (17.2%)
Sepsis	5/153 (3.3%)		8/151 (5.3%)
Cellulitis	9/153 (5.9%)		10/151 (6.6%)
Bacteraemia	12/153 (7.8%)		4/151 (2.6%)
Injury, poisoning and procedural complications
Transfusion Reaction	13/153 (8.5%)		14/151 (9.3%)
Procedural Pain	12/153 (7.8%)		10/151 (6.6%)
Fall	12/153 (7.8%)		8/151 (5.3%)
Contusion	9/153 (5.9%)		11/151 (7.3%)
Investigations
Weight Decreased	5/153 (3.3%)		11/151 (7.3%)
Metabolism and nutrition disorders
Decreased Appetite	50/153 (32.7%)		62/151 (41.1%)
Fluid Overload	13/153 (8.5%)		19/151 (12.6%)
Musculoskeletal and connective tissue disorders
Back Pain	22/153 (14.4%)		21/151 (13.9%)
Pain In Extremity	20/153 (13.1%)		14/151 (9.3%)
Arthralgia	24/153 (15.7%)		9/151 (6%)
Neck Pain	12/153 (7.8%)		8/151 (5.3%)
Musculoskeletal Pain	10/153 (6.5%)		6/151 (4%)
Muscular Weakness	4/153 (2.6%)		11/151 (7.3%)
Myalgia	8/153 (5.2%)		4/151 (2.6%)
Nervous system disorders
Headache	53/153 (34.6%)		37/151 (24.5%)
Dizziness	32/153 (20.9%)		31/151 (20.5%)
Dysgeusia	12/153 (7.8%)		11/151 (7.3%)
Somnolence	3/153 (2%)		9/151 (6%)
Psychiatric disorders
Insomnia	36/153 (23.5%)		38/151 (25.2%)
Confusional State	20/153 (13.1%)		26/151 (17.2%)
Anxiety	23/153 (15%)		22/151 (14.6%)
Delirium	6/153 (3.9%)		13/151 (8.6%)
Depression	10/153 (6.5%)		10/151 (6.6%)
Hallucination	5/153 (3.3%)		8/151 (5.3%)
Agitation	8/153 (5.2%)		4/151 (2.6%)
Renal and urinary disorders
Renal Failure Acute	11/153 (7.2%)		13/151 (8.6%)
Haematuria	10/153 (6.5%)		10/151 (6.6%)
Dysuria	8/153 (5.2%)		10/151 (6.6%)
Pollakiuria	8/153 (5.2%)		8/151 (5.3%)
Urinary Incontinence	9/153 (5.9%)		6/151 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	51/153 (33.3%)		33/151 (21.9%)
Epistaxis	54/153 (35.3%)		27/151 (17.9%)
Dyspnoea	36/153 (23.5%)		32/151 (21.2%)
Hypoxia	30/153 (19.6%)		30/151 (19.9%)
Pleural Effusion	26/153 (17%)		29/151 (19.2%)
Oropharyngeal Pain	28/153 (18.3%)		16/151 (10.6%)
Pulmonary Oedema	12/153 (7.8%)		14/151 (9.3%)
Rales	12/153 (7.8%)		10/151 (6.6%)
Haemoptysis	12/153 (7.8%)		7/151 (4.6%)
Wheezing	11/153 (7.2%)		7/151 (4.6%)
Hiccups	7/153 (4.6%)		9/151 (6%)
Tachypnoea	7/153 (4.6%)		8/151 (5.3%)
Nasal Congestion	9/153 (5.9%)		4/151 (2.6%)
Skin and subcutaneous tissue disorders
Rash	44/153 (28.8%)		33/151 (21.9%)
Petechiae	21/153 (13.7%)		18/151 (11.9%)
Pruritus	23/153 (15%)		13/151 (8.6%)
Rash Maculo-Papular	14/153 (9.2%)		13/151 (8.6%)
Erythema	14/153 (9.2%)		10/151 (6.6%)
Hyperhidrosis	10/153 (6.5%)		13/151 (8.6%)
Night Sweats	14/153 (9.2%)		8/151 (5.3%)
Alopecia	4/153 (2.6%)		17/151 (11.3%)
Blood Blister	14/153 (9.2%)		5/151 (3.3%)
Rash Pruritic	10/153 (6.5%)		6/151 (4%)
Dry Skin	8/153 (5.2%)		7/151 (4.6%)
Rash Erythematous	6/153 (3.9%)		8/151 (5.3%)
Skin Lesion	4/153 (2.6%)		9/151 (6%)
Ecchymosis	9/153 (5.9%)		12/151 (7.9%)
Vascular disorders
Hypotension	30/153 (19.6%)		30/151 (19.9%)
Hypertension	29/153 (19%)		23/151 (15.2%)
Deep Vein Thrombosis	8/153 (5.2%)		9/151 (6%)

Limitations/Caveats

[Not Specified]

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.