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

NCT01696084 | Completed Phase 3 Results DMC

• 1 other identifier: CLTR0310-301
• Study Type: interventional
• Target: 309
• Locations: 2 countries
• Sites: 43

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.

Conditions

High Risk Acute Myeloid Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  From the date of randomization to death from any cause

Secondary Outcomes (5)

• Proportion of Subjects With a Response

  Post Induction

• 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

• Remission Duration

  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

  Day 14

• Proportion of Subjects Receiving a Stem Cell Transplant

  Post Induction

Study Arms (2)

Arm A (CPX-351)

EXPERIMENTAL

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

Arm B (7+3)

ACTIVE COMPARATOR

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

CPX-351 DRUG

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.

Arm A (CPX-351)

7+3 (cytarabine and daunorubicin) DRUG

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

Arm B (7+3)

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (43)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of CA San Diego

San Diego, California, 92037-0706, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Chicago, Illinois, 60208, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Franciscan St. Francis Health

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Missouri

Columbia, Missouri, 65211, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

North Shore LIJ Health System

Long Island City, New York, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cornell U, Weill Medical College

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599-1651, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Services

Winston-Salem, North Carolina, 27157, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15219, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor Research Insitute

Dallas, Texas, 75246, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 770303, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2C8, Canada

Location

British Columbia Cancer Center

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Related Publications (8)

• Shimony S, Murdock HM, Keating JH, Tsai HK, Sasi A, Gibson CJ, Faderl S, Wagner A, Dronamraju N, Lin TL, Prebet T, Cortes JE, Uy GL, Lancet JE, Reilly CR, Neuberg DS, Stone RM, Lindsley RC. CPX-351 Selectively Benefits Patients with AML and Myelodysplasia-Related Mutations in the Pivotal Randomized Trial. Blood Adv. 2026 Feb 2:bloodadvances.2025019378. doi: 10.1182/bloodadvances.2025019378. Online ahead of print.

  PMID: 41628350 DERIVED

• 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.

  PMID: 36289532 DERIVED

• 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.

  PMID: 34256819 DERIVED

• 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.

  PMID: 34171279 DERIVED

• 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.

  PMID: 33724305 DERIVED

• 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.

  PMID: 31760835 DERIVED

• 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.

  PMID: 30024784 DERIVED

• 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.

  PMID: 26660428 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Associate Director, Clinical Trial Disclosure & Transparency
• Organization: Jazz Pharmaceuticals

tom.chmielewski@jazzpharma.com

2158709177

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2012
• First Posted: September 28, 2012
• Study Start: December 13, 2012
• Primary Completion: December 31, 2015
• Study Completion: December 31, 2015
• Last Updated: August 10, 2020
• Results First Posted: October 2, 2017

Record last verified: 2020-07

Locations

US (39); CA (4)