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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01696084
First Posted: September 28, 2012
Last Update Posted: November 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Jazz Pharmaceuticals
  Purpose
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 Intervention Phase
High Risk Acute Myeloid Leukemia Drug: CPX-351 Drug: 7+3 (cytarabine and daunorubicin) Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Jazz Pharmaceuticals:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 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:
  • Proportion of Subjects With a Response [ Time Frame: Post Induction ]
    Complete Remission (CR)

  • Event-free Survival [ 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 ]
    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.

  • Remission Duration [ Time Frame: 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.

  • Rate of Achieving Morphologic Leukemia-free State [ Time Frame: 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.

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


Enrollment: 309
Study Start Date: November 2012
Estimated Study Completion Date: December 2017
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: cytarabine and daunorubicin

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01696084


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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01696084     History of Changes
Other Study ID Numbers: CLTR0310-301
First Submitted: September 26, 2012
First Posted: September 28, 2012
Results First Submitted: September 3, 2017
Results First Posted: October 2, 2017
Last Update Posted: November 21, 2017
Last Verified: October 2017

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
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors