Clinical trial NCT00788892: Trial of CPX-351 in Newly Diagnosed Elderly AML Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Acute
Myeloid
Leukemia
elderly
Newly
Diagnosed
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-11-11
Enrollment: 126
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Complete Remission
timeFrame: Within 6 weeks of the last induction treatment
Secondary outcomes:
measure: Remission Duration/Time to Remission
timeFrame: Following achievement of CR over the study period
measure: Event Free Survival
timeFrame: Up to 1 year from randomization
measure: Overall Survival Rate at 1 Year
timeFrame: 1 year
measure: Rate of Stem Cell Transplant
timeFrame: Up to 1 year
measure: Aplasia Rate
timeFrame: Day 14 (1st Induction)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Jacksonville
country: United States
facility: Shands Jacksonville Medical Center
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Chicago
country: United States
facility: Robert H.Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: St.Francis Hospital
state: Indiana
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Northern New Jersey Cancer Associates
state: New Jersey
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Weil Cornell Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College, Division of Oncology
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center/Mecklenburg Medical Group
state: North Carolina
city: Cincinnati
country: United States
facility: Jewish Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburg Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center at the University of Texas
state: Texas
city: Milwaukee
country: United States
facility: Froedlert Hospital/Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: BC Cancer Research Center
state: British Columbia
city: Halifax
country: Canada
facility: Queen Elisabeth II Health Sciences Center
state: Nova Scotia
city: Montreal
country: Canada
facility: McGill University Department of Oncology
state: Quebec
Study officials:
affiliation: H. Lee Moffitt Cancer Center
name: Jeffrey E Lancet, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.