CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

• Sponsor: Rondeep Brar (Other)
• Overall Status: Completed
• CT.gov ID: NCT02019069
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 11
• Location: 1
• Arm: 1
• Actual Duration (Months): 46.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase 2 clinical trial studies how well CPX-351 (liposomal cytarabine-daunorubicin) works in treating patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes	Drug: liposomal cytarabine-daunorubicin CPX-351	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Determine efficacy of CPX-351 by measuring the response rate as the sum of complete response (CR) and complete remission with incomplete count recovery (CRi) in older patients (age 60 and older) with: higher risk of myelodysplastic syndrome (MDS) who are refractory/relapsed after prior hypomethylating (HMA) therapy; subjects greater than 75 years old with higher risk MDS who are HMA relapsed/refractory who have progressed to acute myeloid leukemia (AML)); AML with refractory/relapsed disease after prior HMA therapy for AML.

SECONDARY OBJECTIVES:

1. Determine the safety of CPX-351, as the frequency of Grade 3 to 5 SAEs

2. Determine the duration of remission (DOR) following induction therapy with CPX-351.

3. Determine overall survival (OS) at 12 months.

4. Determine the early induction mortality (at 30 and 60 days) following CPX-351 following induction therapy.

OUTLINE:

Patients receive liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5 of each induction cycle.

• 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) at day 14 proceed to consolidation therapy

• 2nd INDUCTION: Patients with reduced blast count not achieving a morphological leukemia free state (< 5% blasts) receive the 2nd course of induction therapy. Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. Patients achieving a complete remission (CR) or a CR with incomplete blood count recovery (CRi) after the 2nd course of induction therapy proceed to consolidation therapy.

• CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.

After completion of study treatment, patients are followed up for up to 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of CPX-351 for Treatment of AML or Higher Risk MDS Relapsed or Refractory to Prior Therapy With Hypomethylating (HMA) Agent
• Actual Study Start Date: Feb 3, 2014
• Actual Primary Completion Date: Dec 4, 2017
• Actual Study Completion Date: Dec 18, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Liposomal cytarabine-daunorubicin CPX-351 1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3.

Drug: liposomal cytarabine-daunorubicin CPX-351; Given IV; Other Names: CPX-351

Outcome Measures

Primary Outcome Measures

1. Response Rate (RR) [Day 42]

   The response rate was determined as the sum of complete response calculated by adding the total complete response (CR) and complete response with incomplete count recovery (CRi). The outcome is reported as the total number without dispersion. CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.

Secondary Outcome Measures

1. Complete Response With Incomplete Count Recovery (CRi) [Day 42]

   Complete response (CR) with incomplete count recovery (CRi) was determined as the number of participants who achieved CRi after induction therapy. The outcome is reported as the total number or participants without dispersion. CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.

2. Complete Response (CR) [Day 42]

   Complete response (CR) was determined the number of participants who achieved CR by Day 42 after induction treatment. The outcome is reported as the total number of participants without dispersion. • CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.

3. Duration of Remission (DOR) Following Induction With CPX-351 [Up to 1 year]

   Duration of remission (DOR) was assessed as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until documented lost of response, relapse, or death. The outcome is reported as the median with full range. CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL. For patients remaining alive, duration of remission (DOR) is reported as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until the most recent assessment.

4. Overall Survival (OS) [At 12 months]

   Overall survival (OS) was assessed as the number of participants remaining alive 12 months, starting from date of entry into trial. The outcome is reported as the number of participants (without dispersion).

5. Early Induction Mortality (Day 30 After 1st Induction) [30 days]

   Early induction mortality was assessed as the number of participants who died within 30 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion.

6. Mortality at Day 60 After 1st Induction [60 days]

   Mortality at Day 60 after 1st induction was assessed as the number of participants who died within 60 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion.

7. Participants Experiencing of Serious Adverse Events [Up to 4 weeks after completion of treatment]

   Serious adverse events per participant were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the number of participants that experienced any defined SAE, a number without dispersion.

8. Serious Adverse Events [Up to 4 weeks after completion of treatment]

   Serious adverse events were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the total number of the defined SAEs, a number without dispersion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to understand and voluntarily give informed consent

• Age ≥ 60

• Pathological diagnosis of AML (by WHO criteria) or higher risk MDS (includes int-2 and high risk MDS by IPSS) along with one of the following:

• Patients with de novo or secondary MDS with progression/refractoriness after HMA treatment who have not transformed to AML

• Patients with MDS and prior HMA treatment for MDS who transform to AML

• Patients with AML who are refractory/relapsed after HMA therapy for their AML are eligible

• Life expectancy > 1 month

• 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 ≤ 2.5 mg/dL. Note, patients with Gilbert's syndrome may have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are included if their total bilirubin is ≤ 2 times their baseline total bilirubin.

• Serum alanine aminotransferase or aspartate aminotransferase < 3 times ULN

• Cardiac ejection fraction ≥ 45% by echocardiography (transthoracic echocardiography) or MUGA scan

• Patients with second malignancies may be eligible at discretion of PI given acute life threatening nature of untreated AML or higher risk MDS. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are also eligible.

Exclusion Criteria:

• Patients who have previously undergone allogeneic hematopoietic stem cell transplant will be excluded from this study

• Patients who have previously had > 368 mg/m2 cumulative dose of daunorubicin or > 368 mg/m2 daunorubicin-equivalent anthracycline therapy (for example, from prior treatment of solid tumors). See appendix for anthracycline equivalence table.

• Acute promyelocytic leukemia [t(15;17)]

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

• Patients who have had conventional intensive cytotoxic induction chemotherapy for treatment of specifically MDS or AML are excluded.

• Patients who have not previously been treated with HMA therapy will be excluded

• Clinical evidence of active CNS leukemia

• Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)

• Active and uncontrolled infection. Patients with an active infection receiving treatment and hemodynamically stable for 48 hours may be entered into the study

• Known active uncontrolled HIV or hepatitis C infection

• Known hypersensitivity to cytarabine, daunorubicin or liposomal products

• Known history of Wilson's disease or other copper-related disorders

• Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation

• Laboratory abnormalities:

• Serum creatinine ≥ 2.0 mg/dL

• Serum total bilirubin > 2.5 mg/dL. Note, patients with Gilbert's syndrome may have elevated bilirubin at baseline prior to diagnosis with AML or MDS. Patients with Gilbert's syndrome are excluded if their total bilirubin is > 2 times their baseline total bilirubin.

• Serum alanine aminotransferase or aspartate aminotransferase > 3 times ULN

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University, School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Rondeep Brar
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Rondeep Brar, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 28, 2017

More Information

Publications

None provided.

• Responsible Party: Rondeep Brar, Clinical Assistant Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT02019069
• Other Study ID Numbers: IRB-28524; NCI-2013-01982; HEM0036; P30CA124435
• First Posted: Dec 24, 2013
• Last Update Posted: Jan 22, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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; Preleukemia; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Myelodysplastic Syndromes; Syndrome; Cytarabine; Daunorubicin

Study Results

Participant Flow

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Overall Participants	11
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	11 100%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	74 (4.9)
Sex: Female, Male (Count of Participants)
Female	2 18.2%
Male	9 81.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 18.2%
Not Hispanic or Latino	9 81.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 9.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 72.7%
More than one race	0 0%
Unknown or Not Reported	2 18.2%
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate (RR)
Description	The response rate was determined as the sum of complete response calculated by adding the total complete response (CR) and complete response with incomplete count recovery (CRi). The outcome is reported as the total number without dispersion. CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	3 27.3%

2. Secondary Outcome

Title	Complete Response With Incomplete Count Recovery (CRi)
Description	Complete response (CR) with incomplete count recovery (CRi) was determined as the number of participants who achieved CRi after induction therapy. The outcome is reported as the total number or participants without dispersion. CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	1 9.1%

3. Secondary Outcome

Title	Complete Response (CR)
Description	Complete response (CR) was determined the number of participants who achieved CR by Day 42 after induction treatment. The outcome is reported as the total number of participants without dispersion. • CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence.
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	2 18.2%

4. Secondary Outcome

Title	Duration of Remission (DOR) Following Induction With CPX-351
Description	Duration of remission (DOR) was assessed as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until documented lost of response, relapse, or death. The outcome is reported as the median with full range. CR = less than 5% blasts; no blasts with auer rods; and no persistence of extramedullary disease, with blood count recovery to platelets ≥ 100,000/uL and ANC > 1000/uL, with transfusion independence. CRi = all the parameters for CR, but platelets < 100,000/uL and/or ANC ≤ 1000/uL. For patients remaining alive, duration of remission (DOR) is reported as the length of time from documented complete response (CR) or complete response with incomplete count recovery (CRi) until the most recent assessment.
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Median (Full Range) [days]	185

5. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) was assessed as the number of participants remaining alive 12 months, starting from date of entry into trial. The outcome is reported as the number of participants (without dispersion).
Time Frame	At 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	1 9.1%

6. Secondary Outcome

Title	Early Induction Mortality (Day 30 After 1st Induction)
Description	Early induction mortality was assessed as the number of participants who died within 30 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	2 18.2%

7. Secondary Outcome

Title	Mortality at Day 60 After 1st Induction
Description	Mortality at Day 60 after 1st induction was assessed as the number of participants who died within 60 days of completing the 1st cycle of CPX-351 (1st induction). The outcome is reported as the number of participants without dispersion.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	3 27.3%

8. Secondary Outcome

Title	Participants Experiencing of Serious Adverse Events
Description	Serious adverse events per participant were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the number of participants that experienced any defined SAE, a number without dispersion.
Time Frame	Up to 4 weeks after completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Count of Participants [Participants]	5 45.5%

9. Secondary Outcome

Title	Serious Adverse Events
Description	Serious adverse events were assessed as serious adverse events per 21CFR§312.32 that were Grade 3 or greater, and independent of relationship to CPX-351. The outcome is reported as the total number of the defined SAEs, a number without dispersion.
Time Frame	Up to 4 weeks after completion of treatment

Outcome Measure Data

Analysis Population Description

Per protocol, the outcome only includes SAEs that are Grade 3 or greater. Adverse events that were Grade 2 or less, (eg, Grade 2 event with hospitalization) are not included.

Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
Measure Participants	11
Number [Adverse events]	8

Adverse Events

Time Frame	Up to 4 weeks after completion of treatment]
Arm/Group Title	Liposomal Cytarabine-daunorubicin CPX-351
Arm/Group Description	1st INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV at a dose of 65 units/m2/day over 90 minutes on days 1, 3, and 5. 2nd INDUCTION: Patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. CONSOLIDATION: Beginning on day 28, patients receive liposomal cytarabine-daunorubicin CPX-351 IV a dose of 65 units/m2/day over 90 minutes on days 1 and 3. liposomal cytarabine-daunorubicin CPX-351: Given IV
All Cause Mortality
	Liposomal Cytarabine-daunorubicin CPX-351
	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)
Serious Adverse Events
	Liposomal Cytarabine-daunorubicin CPX-351
	Affected / at Risk (%)	# Events
Total	5/11 (45.5%)
Blood and lymphatic system disorders
Febrile neutropenia	4/11 (36.4%)	5
Anemia	1/11 (9.1%)	1
Cardiac disorders
Cardio-pulmonary arrest	1/11 (9.1%)	1
General disorders
Chills	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms - Other, Acute myelogenous leukemia	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	2/11 (18.2%)	2
Adult repiratory distress syndrome (ARDS)	1/11 (9.1%)	1
Respiratory failure	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Liposomal Cytarabine-daunorubicin CPX-351
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders, other - clot in cheek	1/11 (9.1%)	1
Febrile neutropenia	8/11 (72.7%)	8
Thrombotic thrombocytopenic purpura	2/11 (18.2%)	2
Cardiac disorders
Atrial fibrillation	1/11 (9.1%)	1
Cardiac disorders, other - tachycardia	1/11 (9.1%)	1
Sinus tachycardia	1/11 (9.1%)	1
Eye disorders
Eye disorders, other - eye itching	1/11 (9.1%)	1
Papilledema	1/11 (9.1%)	1
Gastrointestinal disorders
Abdominal pain	3/11 (27.3%)	3
Colitis	3/11 (27.3%)	3
Constipation	4/11 (36.4%)	4
Diarrhea	7/11 (63.6%)	7
Mucositis oral	6/11 (54.5%)	6
Nausea	1/11 (9.1%)	1
Rectal hemorrhage	1/11 (9.1%)	1
General disorders
Pain, hip	1/11 (9.1%)	1
Pain, leg	1/11 (9.1%)	1
Fatigue	1/11 (9.1%)	1
Fever	4/11 (36.4%)	4
Infections and infestations
Lung infection	2/11 (18.2%)	2
Investigations
Alanine aminotransferase increased	2/11 (18.2%)	2
Investigations, other - fluid overload	1/11 (9.1%)	1
Metabolism and nutrition disorders
Hepatobiliary disorders, other - hyperbilirubinemia	1/11 (9.1%)	1
Anorexia (decreased food consumption)	1/11 (9.1%)	1
Hypertriglyceridemia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorder, other - broken leg	1/11 (9.1%)	1
Nervous system disorders
Brachial plexopathy	1/11 (9.1%)	1
Dizziness	2/11 (18.2%)	2
Headache	1/11 (9.1%)	1
Peripheral motor neuropathy	1/11 (9.1%)	1
Psychiatric disorders
Hallucinations	4/11 (36.4%)	4
Renal and urinary disorders
Hematuria	3/11 (27.3%)	3
Renal and urinary disorders, other - urinary discomfort	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	1/11 (9.1%)	1
Cough	3/11 (27.3%)	3
Epistaxis (nose bleed)	1/11 (9.1%)	1
Hypoxia	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders, other - chest tightness	1/11 (9.1%)	1
Pneumothorax	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Rash	3/11 (27.3%)	3
Skin and subcutaneous tissue disorders, other - multiple subcutaneous nodules	1/11 (9.1%)	1
Vascular disorders
Thromboembolic event	1/11 (9.1%)	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.