Trial of CPX-351 in Newly Diagnosed Elderly AML Patients

Phase IIB, Multicenter, Randomized, Open Label Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients With Untreated AML 60-75 Years of Age.

The study investigates if CPX-351 will be a) more effective than the standard AML treatment and b) more tolerable than the standard AML treatment regimens.

The study compares the investigational product CPX-351 vs the standard treatment for AML in this patients age group.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: CPX-351; Drug: Cytarabine; Drug: Daunorubicin

Detailed Description

This study is a randomized, open-label, parallel-arm, fixed-dose, standard therapy controlled Phase IIB trial. Study enrollment duration is expected to be approximately 12-18 months. On entry, patients are randomized to receive either CPX-351 or standard induction treatment with cytarabine and daunorubicin("7 and 3" regimen).

Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR between the two arms.

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L3
      • BC Cancer Research Center
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen elisabeth II Health Sciences Center
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • McGill University Department of Oncology
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Cancer Center
    • San Francisco, California, United States, 94143
      • University of California Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Shands Jacksonville Medical Center
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Blood and Marrow Transplant Group of Georgia
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Robert H.Lurie Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612-3861
      • Rush University Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St.Francis Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Northern New Jersey Cancer Associates
  • New York
    • Manhasset, New York, United States, 11020
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Weil Cornell Medical Center
    • Valhalla, New York, United States, 10595
      • New York Medical College, Division of Oncology
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Blumenthal Cancer Center/Mecklenburg Medical Group
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Jewish Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburg Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Center
    • Lubbock, Texas, United States, 79415
      • Texas Tech University Health Sciences Center
    • San Antonio, Texas, United States, 78229
      • Cancer Therapy and Research Center at the University of Texas
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedlert Hospital/Medical College of Wisconsin

Participation Criteria

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:

• Age ≥60 and <76 years at the time of diagnosis of AML
• Pathological confirmation of AML
• 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 Serum alanine aminotransferase or aspartate aminotransferase < 150 IU/liter Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss.

• Cardiac ejection fraction > 50% by echocardiography or MUGA scan

Exclusion Criteria:

• Patients with locally advanced or metastatic solid tumors ≤5 years from initial diagnosis are excluded. (Patients with locally advanced or metastatic solid tumors >5 years from initial diagnosis, for whom the investigator has no clinical suspicion of active disease for >2 years before randomization are eligible)
• Prior treatment for AML; only hydroxyurea is permitted (see below)
• Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization
• Patients with a prior 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
• Administration of any antineoplastic therapy within 4 weeks of the first CPX-351 dose; in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment
• Clinical evidence of active CNS leukemia
• Patients with history of and/or current evidence of myocardial impairment (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 Class III or IV staging
• Active and uncontrolled infection. Patients with an infection receiving treatment with antibiotics may be entered into the study if they are afebrile and hemodynamically stable for 72 hrs.
• Current evidence of invasive fungal infection (blood or tissue culture); HIV or active hepatitis C infection
• Hypersensitivity to cytarabine, daunorubicin or liposomal products
• History of Wilson's disease or other copper-related disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: CPX-351; First induction: CPX-351 at 100u/m2 administered on days 1, 3 and 5 Second induction: CPX-351 at 100u/m2 administered on days 1 and 3 Consolidation: CPX-351 at 100u/m2 administered on days 1 and 3	Drug: CPX-351
Active Comparator: Arm B: Cytarabine + Daunorubicin; First induction: Cytarabine at a dose of 100mg/m2/day on days 1-7, Daunorubicin at dose of 45 or 60mg/m2 on days 1-3 Second induction: Cytarabine at a dose of 100mg/m2/day on days 1-5, Daunorubicin at a dose of 45 or 60 mg/m2/day on days 1 and 2 Consolidation: Investigator's Choice	Drug: Cytarabine; Drug: Daunorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Complete Remission	Response was defined according to International Working Group Criteria (Cheson, et al. 2003) which requires peripheral blood neutrophils of >1000/µL and peripheral blood platelets of >100,000/µL in the absence of bone marrow blasts.	Within 6 weeks of the last induction treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission Duration/Time to Remission	Remission Duration was assessed from the time measurement criteria for CR were met until the first date that disease relapse was objectively documented or the subject died. Time to remission was measured from the date of randomization to the time measurement criteria for CR were first met.	Following achievement of CR over the study period
Event Free Survival	Event-free survival begins from randomization to the date persistent disease is documented or date of relapse after CR, or death, whichever comes first.	Up to 1 year from randomization
Overall Survival Rate at 1 Year	Survival defined as the time from randomization to death.	1 year
Rate of Stem Cell Transplant	The rate of patients who underwent stem cell transplant.	Up to 1 year
Aplasia Rate	Bone marrow aplasia was defined as <20% cellularity and 5% blasts in the bone marrow aspiration evaluation.	Day 14 (1st Induction)

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Investigators: Principal Investigator: Jeffrey E Lancet, MD, H. Lee Moffitt Cancer Center

Publications and helpful links

General Publications

• Lancet JE, Cortes JE, Hogge DE, Tallman MS, Kovacsovics TJ, Damon LE, Komrokji R, Solomon SR, Kolitz JE, Cooper M, Yeager AM, Louie AC, Feldman EJ. Phase 2 trial of CPX-351, a fixed 5:1 molar ratio of cytarabine/daunorubicin, vs cytarabine/daunorubicin in older adults with untreated AML. Blood. 2014 May 22;123(21):3239-46. doi: 10.1182/blood-2013-12-540971. Epub 2014 Mar 31.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: November 10, 2008
• First Submitted That Met QC Criteria: November 10, 2008
• First Posted (Estimate): November 11, 2008

Study Record Updates

• Last Update Posted (Actual): January 12, 2018
• Last Update Submitted That Met QC Criteria: December 15, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: elderly; Leukemia; Acute; Myeloid; Newly; Diagnosed
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cytarabine; Daunorubicin
• Other Study ID Numbers: CLTR0308-204