CompletedNCT01696084301Updated Aug 10, 2020Results posted

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

A Phase 3 interventional study of CPX-351 and 7+3 (cytarabine and daunorubicin) in High Risk Acute Myeloid Leukemia, sponsored by Jazz Pharmaceuticals. Completed at 43 sites in 2 countries. Open to participants aged 60 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-08-10.

Sponsored by Jazz Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 309
Allocation: Randomized
Ages: 60 Years to 75 Years
Sex: All

Study 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.

Conditions studied

High Risk Acute Myeloid Leukemia

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Keywords

AML
Acute Myeloid Leukemia
high risk AML
secondary AML
AML in elderly

In context

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 309 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

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Lead sponsor

Jazz Pharmaceuticals is the lead sponsor of 167 studies on the registry; 20 are open to participants now.

Of its 39 completed or terminated interventional studies of FDA-regulated products, 28 (72%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 60 Years to 75 Years
Sexes eligible: 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

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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 309 participants (actual)

Study arms

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
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)

Interventions

DrugCPX-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.
Drug7+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.
Also known as: cytarabine and daunorubicin

What researchers measure

Primary outcomes

Overall Survival
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

Secondary outcomes

Proportion of Subjects With a Response
Complete Remission (CR)
Time frame: Post Induction
Event-free Survival
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
Remission Duration
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
Rate of Achieving Morphologic Leukemia-free State
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
Proportion of Subjects Receiving a Stem Cell Transplant
The number and percentage of subjects transferred for HSCT after induction treatment was recorded.
Time frame: Post Induction

Results

Posted Oct 2, 2017

Participant flow

Participant flow — Overall Study
Milestone	Arm A (CPX-351)	Arm B (7+3)
Started	153	156
Completed	22	10
Not completed	131	146

Outcome measures

PrimaryOverall Survival

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
Reported as:: Median · months

Overall Survival
months	Arm A (CPX-351)	Arm B (7+3)
Overall Survival	9.56 (6.60 to 11.86)	5.95 (4.99 to 7.75)

SecondaryProportion of Subjects With a Response

Complete Remission (CR)

Time frame:: Post Induction
Reported as:: Count of participants · Participants

Proportion of Subjects With a Response
Participants	Arm A (CPX-351)	Arm B (7+3)
Proportion of Subjects With a Response	57	40

SecondaryEvent-free Survival

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
Reported as:: Median · months

Event-free Survival
months	Arm A (CPX-351)	Arm B (7+3)
Event-free Survival	2.53 (2.07 to 4.99)	1.31 (1.08 to 1.64)

SecondaryRemission Duration

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
Reported as:: Median · months

Remission Duration
months	Arm A (CPX-351)	Arm B (7+3)
Remission Duration	6.93 (4.60 to 9.23)	6.11 (3.45 to 8.71)

SecondaryRate of Achieving Morphologic Leukemia-free State

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
Reported as:: Count of participants · Participants

Rate of Achieving Morphologic Leukemia-free State
Participants	Arm A (CPX-351)	Arm B (7+3)
Rate of Achieving Morphologic Leukemia-free State	87	66

SecondaryProportion of Subjects Receiving a Stem Cell Transplant

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

Time frame:: Post Induction
Reported as:: Count of participants · Participants

Proportion of Subjects Receiving a Stem Cell Transplant
Participants	Arm A (CPX-351)	Arm B (7+3)
Proportion of Subjects Receiving a Stem Cell Transplant	52	39

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm A (CPX-351)	1/153 (0.7%)	90/153 (58.8%)	152/153 (99.3%)
Arm B (7+3)	0/151 (0%)	65/151 (43%)	151/151 (100%)

Most frequent serious events

Showing 10 of 128

Most frequent serious events
Event	Arm A (CPX-351)	Arm B (7+3)
Febrile NeutropeniaBlood and lymphatic system disorders	12/153	8/151
SepsisInfections and infestations	12/153	5/151
Respiratory FailureRespiratory, thoracic and mediastinal disorders	11/153	8/151
PneumoniaInfections and infestations	10/153	6/151
Ejection Fraction DecreasedInvestigations	9/153	9/151
Disease ProgressionGeneral disorders	6/153	6/151
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders	6/153	3/151
Left Ventricular DysfunctionCardiac disorders	0/153	4/151
Multi-Organ FailureGeneral disorders	2/153	4/151
BacteraemiaInfections and infestations	4/153	0/151

Most frequent other events

Showing 10 of 97

Most frequent other events
Event	Arm A (CPX-351)	Arm B (7+3)
Febrile NeutropeniaBlood and lymphatic system disorders	104/153	105/151
DiarrhoeaGastrointestinal disorders	70/153	103/151
NauseaGastrointestinal disorders	75/153	83/151
Oedema PeripheralGeneral disorders	62/153	76/151
ConstipationGastrointestinal disorders	65/153	60/151
Decreased AppetiteMetabolism and nutrition disorders	50/153	62/151
EpistaxisRespiratory, thoracic and mediastinal disorders	54/153	27/151
FatigueGeneral disorders	53/153	53/151
HeadacheNervous system disorders	53/153	37/151
CoughRespiratory, thoracic and mediastinal disorders	51/153	33/151

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Arm A (CPX-351)	Arm B (7+3)	Total
Mean	67.8 ± 4.19	67.7 ± 4.1	67.7 ± 4.14

Sex: Female, Male
Sex: Female, Male(Participants)	Arm A (CPX-351)	Arm B (7+3)	Total
Female	59	60	119
Male	94	96	190

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Arm A (CPX-351)	Arm B (7+3)	Total
American Indian or Alaska Native	1	0	1
Asian	6	2	8
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	7	6	13
White	128	139	267
More than one race	0	1	1
Unknown or Not Reported	11	8	19

Study locations

43 sites

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

References and documents

Publications

Cortes JE, Lin TL, Asubonteng K, Faderl S, Lancet JE, Prebet T. Efficacy and safety of CPX-351 versus 7 + 3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial. J Hematol Oncol. 2022 Oct 26;15(1):155. doi: 10.1186/s13045-022-01361-w. PubMed 36289532 ↗
Cortes JE, Lin TL, Uy GL, Ryan RJ, Faderl S, Lancet JE. Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML. J Hematol Oncol. 2021 Jul 13;14(1):110. doi: 10.1186/s13045-021-01119-w. PubMed 34256819 ↗
Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Faderl S, Cortes JE. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021 Jul;8(7):e481-e491. doi: 10.1016/S2352-3026(21)00134-4. PubMed 34171279 ↗
Lin TL, Rizzieri DA, Ryan DH, Schiller GJ, Kolitz JE, Uy GL, Hogge DE, Solomon SR, Wieduwilt MJ, Ryan RJ, Faderl S, Cortes JE, Lancet JE. Older adults with newly diagnosed high-risk/secondary AML who achieved remission with CPX-351: phase 3 post hoc analyses. Blood Adv. 2021 Mar 23;5(6):1719-1728. doi: 10.1182/bloodadvances.2020003510. PubMed 33724305 ↗
Kolitz JE, Strickland SA, Cortes JE, Hogge D, Lancet JE, Goldberg SL, Villa KF, Ryan RJ, Chiarella M, Louie AC, Ritchie EK, Stuart RK. Consolidation outcomes in CPX-351 versus cytarabine/daunorubicin-treated older patients with high-risk/secondary acute myeloid leukemia. Leuk Lymphoma. 2020 Mar;61(3):631-640. doi: 10.1080/10428194.2019.1688320. Epub 2019 Nov 25. PubMed 31760835 ↗
Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia. J Clin Oncol. 2018 Sep 10;36(26):2684-2692. doi: 10.1200/JCO.2017.77.6112. Epub 2018 Jul 19. PubMed 30024784 ↗
Stein EM, Tallman MS. Emerging therapeutic drugs for AML. Blood. 2016 Jan 7;127(1):71-8. doi: 10.1182/blood-2015-07-604538. Epub 2015 Dec 10. PubMed 26660428 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 10, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01696084
Lead sponsor: Jazz Pharmaceuticals
Collaborators: The Leukemia and Lymphoma Society
Responsible party: Sponsor
First posted: Sep 28, 2012
Start date: Dec 13, 2012
Primary completion: Dec 31, 2015
Completion: Dec 31, 2015
Results posted: Oct 2, 2017
Last update: Aug 10, 2020

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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