CPX-351 in Treating Patients With Newly Diagnosed, High-Risk Acute Myeloid Leukemia

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02286726
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 56
• Location: 1
• Arms: 3
• Actual Duration (Months): 56.6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This phase II trial studies the best dose and how well liposomal cytarabine-daunorubicin CPX-351 (CPX-351) works in treating patients with newly diagnosed acute myeloid leukemia and who are at risk for not responding well to treatment. Liposomal cytarabine-daunorubicin CPX-351 combines two chemotherapy drugs that are known to help each other work better, and may work to stop the growth of cancer cells by blocking the cells from dividing.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Secondary Acute Myeloid Leukemia	Other: Laboratory Biomarker Analysis; Drug: Liposome-encapsulated Daunorubicin-Cytarabine	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. To assess preliminary efficacy (as determined by the rate of complete response [CR] or CR with incomplete blood count recovery [CRi]) of two or three dose levels of CPX-351 in patients with newly diagnosed acute myeloid leukemia (AML) at high risk for induction mortality, defined as 30-50% predicted risk of death by day 60, and to select the most promising dose level for further efficacy testing.

SECONDARY OBJECTIVE:

1. To confirm the rate of dose limiting toxicities, including induction mortality (at day 60) for two different sub-maximum tolerated dose (MTD) dose levels (50 and 75 U/m^2).

EXPLORATORY OBJECTIVES:

1. To investigate the effect of CPX-351 on immune response, as determined by the effect on recovery of functional pathogen-specific and leukemia-specific immune responses and the recovery and function of natural killer (NK) cells.

2. To investigate the role of troponin-T as an early marker for CPX-351-induced cardiotoxicity.

3. To investigate ex vivo the cytotoxicity of combination of Pim-1 proto-oncogene, serine/threonine kinase (Pim) kinase inhibitor(s) and CPX-351 on circulating leukemia cells.

OUTLINE:

INDUCTION: Patients are randomized to 1 of 2 arms. After safety is established for both dose levels, and escalation is deemed feasible, an additional arm will be studied at the standard dose level.

ARM I: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3.

ARM II: Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.

ARM III: Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.

CONSOLIDATION THERAPY: Patients achieving CR receive liposomal cytarabine-daunorubicin CPX-351 on days 1 and 3. Treatment may repeat every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly for as long as the study doctor thinks it is needed, every 2-3 months for up to 1 year, and every 3-4 months for up to 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Patients With Newly Diagnosed AML at High Risk for Induction Mortality
• Actual Study Start Date: May 4, 2015
• Actual Primary Completion Date: Jan 22, 2020
• Actual Study Completion Date: Jan 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (lower-dose (50 units/m^2) CPX-351) Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351 Cytarabine-Daunorubicin Liposome for Injection Liposomal AraC-Daunorubicin CPX-351 Liposomal Cytarabine-Daunorubicin Liposome-encapsulated Combination of Daunorubicin and Cytarabine Vyxeos
Experimental: Arm II (intermediate-dose (75 units/m^2) CPX-351) Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351 Cytarabine-Daunorubicin Liposome for Injection Liposomal AraC-Daunorubicin CPX-351 Liposomal Cytarabine-Daunorubicin Liposome-encapsulated Combination of Daunorubicin and Cytarabine Vyxeos
Experimental: Arm III (standard-dose (100 units/m^2) CPX-351) Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Given IV; Other Names: CPX-351 Cytarabine-Daunorubicin Liposome for Injection Liposomal AraC-Daunorubicin CPX-351 Liposomal Cytarabine-Daunorubicin Liposome-encapsulated Combination of Daunorubicin and Cytarabine Vyxeos

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Response [Up to 8 weeks (after induction therapy)]

   Response is defined as Complete response (CR) or CR with incomplete blood count recovery (CRi) rate: Complete Remission (CR) is Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 10^9/L (1000/μL); platelet count >100 x 10^9/L (100,000/μL). Complete Response with incomplete blood count recovery (CRi) is All CR criteria except for residual neutropenia (<1.0 x 10^9/L [1000/μL]) and/or thrombocytopenia (<100 x 10^9/L [100,000/μL]).

Secondary Outcome Measures

1. Number of Participants Who Experienced Dose-limiting Toxicity (DLT) [Up to day 60]

   Defined as induction mortality (death occurring on or before day 60), grade 3 or 4 non-hematologic toxicity, or dose limiting hematologic toxicity at least possibly related to the study drug occurring during the first 28 days from the start of therapy. Estimated for each arm with 95% confidence intervals. Fisher's exact test will be used to compare the toxicity rate between the two dose levels.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Ability to understand and voluntarily sign an informed consent form

• Pathological diagnosis of AML according to World Health Organization (WHO) criteria (with at least 20% blasts in the peripheral blood or bone marrow): newly diagnosed de novo AML; except for acute promyelocytic leukemia (APL); newly diagnosed secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease [MPD] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de novo AML with MDS-associated karyotype

• Eastern Cooperative Oncology Group (ECOG) performance status 0-3

• Serum creatinine =< 2.0 mg/dL

• Serum total bilirubin =< 2.0 mg/dL

• Serum alanine aminotransferase < 3 times the upper limit of normal (ULN); Note: If elevated liver enzymes are related to disease alanine aminotransferase (ALT) should be < 5 times ULN

• To be considered at high risk for induction mortality patients must have 1 or 2 of the following risk factors (patients >= 60 must have at least 1 risk factor, patients < 60 must have at least 2 risk factors) present; at least one risk factor in every patient must be an AML-related factor:

• AML-related factors include:

• Antecedent hematologic disorder (AHD) (MDS, chronic myelomonocytic leukemia [CMML], or MPD) or history of exposure to cytotoxic chemotherapy [therapy-related (t)-AML]), or WHO-defined AML with MDS-related changes or apparent de novo AML with MDS-associated karyotype

• Unfavorable cytogenetics as defined by the European Leukemia Net

• Patient-related factors:

• Age >= 70

• ECOG performance status (PS) >= 2

• Co-morbidities:

• Serum creatinine > 1.3 g/dL

• Cardiac ejection fraction >= 50% by echocardiography or multi gated acquisition (MUGA) (when left ventricular ejection fraction [LVEF] expressed as a range, at least the upper limit should include 50%)

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

• All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile

Exclusion Criteria:

• Patients with history of second malignancy are eligible if they have documentation of disease stability, off therapy, based on computed tomography (CT) scan or other measures for the 6 months prior to entry in core

• Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent

• Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks prior to study entry; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 24 hours before study entry in core

• Evidence of active central nervous system (CNS) leukemia

• Pregnant or lactating women

• Uncontrolled infection; to be eligible, patients receiving treatment for an infection (antibiotic, antifungal or antiviral treatment) must be afebrile (< 38.3 degrees Celsius [C]) and without hemodynamic instability or dyspnea from pneumonia for > 48 hours (hrs) prior to the start of induction therapy

• 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	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ghayas Issa, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 9, 2019

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02286726
• Other Study ID Numbers: 2014-0548; NCI-2014-02529; 2014-0548
• First Posted: Nov 10, 2014
• Last Update Posted: Jan 14, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Cytarabine; Daunorubicin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 2015 to January 2020

Arm/Group Title	Arm I (Lower-dose (50 Units/m^2) CPX-351)	Arm II (Intermediate-dose (75 Units/m^2) CPX-351)	Arm III (Standard-dose (100 Units/m^2) CPX-351)
Arm/Group Description	Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Period Title: Overall Study
STARTED	16	24	16
COMPLETED	16	24	16
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Arm I (Lower-dose (50 Units/m^2) CPX-351)	Arm II (Intermediate-dose (75 Units/m^2) CPX-351)	Arm III (Standard-dose (100 Units/m^2) CPX-351)	Total
Arm/Group Description	Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Total of all reporting groups
Overall Participants	16	24	16	56
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 50%	9 37.5%	5 31.3%	22 39.3%
>=65 years	8 50%	15 62.5%	11 68.8%	34 60.7%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63	66	69	67
Sex: Female, Male (Count of Participants)
Female	7 43.8%	8 33.3%	4 25%	19 33.9%
Male	9 56.3%	16 66.7%	12 75%	37 66.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 6.3%	0 0%	0 0%	1 1.8%
White	14 87.5%	24 100%	16 100%	54 96.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 6.3%	0 0%	0 0%	1 1.8%
Region of Enrollment (participants) [Number]
United States	16 100%	24 100%	16 100%	56 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Response
Description	Response is defined as Complete response (CR) or CR with incomplete blood count recovery (CRi) rate: Complete Remission (CR) is Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 10^9/L (1000/μL); platelet count >100 x 10^9/L (100,000/μL). Complete Response with incomplete blood count recovery (CRi) is All CR criteria except for residual neutropenia (<1.0 x 10^9/L [1000/μL]) and/or thrombocytopenia (<100 x 10^9/L [100,000/μL]).
Time Frame	Up to 8 weeks (after induction therapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lower-dose (50 Units/m^2) CPX-351)	Arm II (Intermediate-dose (75 Units/m^2) CPX-351)	Arm III (Standard-dose (100 Units/m^2) CPX-351)
Arm/Group Description	Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Measure Participants	16	24	16
Complete Response (CR)	3 18.8%	6 25%	7 43.8%
Complete Response with incomplete blood count recovery (CRi)	0 0%	3 12.5%	0 0%

2. Secondary Outcome

Title	Number of Participants Who Experienced Dose-limiting Toxicity (DLT)
Description	Defined as induction mortality (death occurring on or before day 60), grade 3 or 4 non-hematologic toxicity, or dose limiting hematologic toxicity at least possibly related to the study drug occurring during the first 28 days from the start of therapy. Estimated for each arm with 95% confidence intervals. Fisher's exact test will be used to compare the toxicity rate between the two dose levels.
Time Frame	Up to day 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I (Lower-dose (50 Units/m^2) CPX-351)	Arm II (Intermediate-dose (75 Units/m^2) CPX-351)	Arm III (Standard-dose (100 Units/m^2) CPX-351)
Arm/Group Description	Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV	Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
Measure Participants	16	24	16
Count of Participants [Participants]	5 31.3%	3 12.5%	3 18.8%

Adverse Events

Time Frame	up to 4 years
Arm/Group Title	Arm I (Lower-dose (50 Units/m^2) CPX-351)		Arm II (Intermediate-dose (75 Units/m^2) CPX-351)		Arm III (Standard-dose (100 Units/m^2) CPX-351)
Arm/Group Description	Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV		Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV		Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3. Laboratory Biomarker Analysis: Correlative studies Liposome-encapsulated Daunorubicin-Cytarabine: Given IV
All Cause Mortality
	Arm I (Lower-dose (50 Units/m^2) CPX-351)		Arm II (Intermediate-dose (75 Units/m^2) CPX-351)		Arm III (Standard-dose (100 Units/m^2) CPX-351)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)		3/24 (12.5%)		4/16 (25%)
Serious Adverse Events
	Arm I (Lower-dose (50 Units/m^2) CPX-351)		Arm II (Intermediate-dose (75 Units/m^2) CPX-351)		Arm III (Standard-dose (100 Units/m^2) CPX-351)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/16 (68.8%)		15/24 (62.5%)		11/16 (68.8%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/16 (6.3%)	2	6/24 (25%)	7	2/16 (12.5%)	2
Cardiac disorders
Acute Coronary Syndrome	0/16 (0%)	0	1/24 (4.2%)	1	0/16 (0%)	0
Cardiac Arrest	1/16 (6.3%)	1	0/24 (0%)	0	0/16 (0%)	0
Gastrointestinal disorders
Pancreatitis	0/16 (0%)	0	1/24 (4.2%)	1	0/16 (0%)	0
Gastrointestinal Disorders	1/16 (6.3%)	1	0/24 (0%)	0	1/16 (6.3%)	1
General disorders
Abdominal Pain	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Back Pain	1/16 (6.3%)	1	0/24 (0%)	0	0/16 (0%)	0
Death	2/16 (12.5%)	2	0/24 (0%)	0	0/16 (0%)	0
Fever	3/16 (18.8%)	6	1/24 (4.2%)	1	1/16 (6.3%)	2
Multi-Organ Failure	0/16 (0%)	0	1/24 (4.2%)	1	1/16 (6.3%)	1
Infections and infestations
Infection Right Arm Abcess	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Infection	1/16 (6.3%)	1	2/24 (8.3%)	3	4/16 (25%)	4
Lung Infection	2/16 (12.5%)	2	4/24 (16.7%)	6	4/16 (25%)	5
Orbital Cellulitis	1/16 (6.3%)	1	0/24 (0%)	0	0/16 (0%)	0
Sepsis	1/16 (6.3%)	1	4/24 (16.7%)	4	1/16 (6.3%)	1
Injury, poisoning and procedural complications
Fall	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	2
Musculoskeletal and connective tissue disorders
Joint Effusion	0/16 (0%)	0	1/24 (4.2%)	1	0/16 (0%)	0
Nervous system disorders
Intracranial Hemorrhage	1/16 (6.3%)	1	1/24 (4.2%)	1	1/16 (6.3%)	1
Reproductive system and breast disorders
Reproductive System and Breast Disorders	1/16 (6.3%)	1	0/24 (0%)	0	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Pleural Effusion	0/16 (0%)	0	1/24 (4.2%)	1	0/16 (0%)	0
Respiratory Failure	0/16 (0%)	0	1/24 (4.2%)	1	2/16 (12.5%)	2
Sore Throat	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Vascular disorders
Hypertension	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Hypotension	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Lower-dose (50 Units/m^2) CPX-351)		Arm II (Intermediate-dose (75 Units/m^2) CPX-351)		Arm III (Standard-dose (100 Units/m^2) CPX-351)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		11/24 (45.8%)		10/16 (62.5%)
Blood and lymphatic system disorders
Neutropenic Fever	0/16 (0%)	0	5/24 (20.8%)	5	2/16 (12.5%)	2
Cardiac disorders
Cardiac Disorders	0/16 (0%)	0	1/24 (4.2%)	1	3/16 (18.8%)	3
Pericardial Effusion	0/16 (0%)	0	2/24 (8.3%)	2	0/16 (0%)	0
Gastrointestinal disorders
Gastric Hemorrhage	0/16 (0%)	0	0/24 (0%)	0	2/16 (12.5%)	2
Gastrointestinal Disorders	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Mucositis	0/16 (0%)	0	0/24 (0%)	0	3/16 (18.8%)	3
General disorders
Fever	0/16 (0%)	0	1/24 (4.2%)	1	1/16 (6.3%)	1
Headache	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Infections and infestations
Infection	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Lung Infection	0/16 (0%)	0	4/24 (16.7%)	4	4/16 (25%)	4
Sepsis	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Urinary Tract Infection	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	2
Injury, poisoning and procedural complications
Fall	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Injury	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Investigations
Alanine aminotransferase Increase	0/16 (0%)	0	1/24 (4.2%)	1	1/16 (6.3%)	1
Blood Bilirubin Increase	0/16 (0%)	0	1/24 (4.2%)	1	2/16 (12.5%)	2
Ejection Fraction Decreased	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Investigation	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Metabolism and nutrition disorders
Hyperkalemia	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal and Connective Tissue Disorder	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Psychiatric disorders
Anxiety	0/16 (0%)	0	1/24 (4.2%)	1	2/16 (12.5%)	2
Insomnia	0/16 (0%)	0	3/24 (12.5%)	3	0/16 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Allergic Rhinitis	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Respiratory Failure	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Sore throat	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Vascular disorders
Hypertension	0/16 (0%)	0	2/24 (8.3%)	2	1/16 (6.3%)	1
Thromboembolic event	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1
Vascular Disorders	0/16 (0%)	0	0/24 (0%)	0	1/16 (6.3%)	1

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.