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

July 28, 2020 updated by: Jazz Pharmaceuticals

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

309

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • cytarabine and daunorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From the date of randomization to death from any cause

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Subjects With a Response
Time Frame: Post Induction
Complete Remission (CR)
Post Induction
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.
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
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.
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
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.
Day 14
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.
Post Induction

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jazz Pharmaceuticals

Collaborators

The Leukemia and Lymphoma Society

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 13, 2012

Primary Completion (ACTUAL)

December 31, 2015

Study Completion (ACTUAL)

December 31, 2015

Study Registration Dates

First Submitted

September 26, 2012

First Submitted That Met QC Criteria

September 27, 2012

First Posted (ESTIMATE)

September 28, 2012

Study Record Updates

Last Update Posted (ACTUAL)

August 10, 2020

Last Update Submitted That Met QC Criteria

July 28, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLTR0310-301

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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