Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia
- Conditions
- High Risk Acute Myeloid Leukemia
- Interventions
- Drug: 7+3 (cytarabine and daunorubicin)
- Registration Number
- NCT01696084
- Lead Sponsor
- Jazz Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 309
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B (7+3) 7+3 (cytarabine and daunorubicin) 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. Arm A (CPX-351) 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.
- Primary Outcome Measures
Name Time Method Overall Survival 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
Name Time Method Proportion of Subjects With a Response Post Induction Complete Remission (CR)
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 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 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 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 Post Induction The number and percentage of subjects transferred for HSCT after induction treatment was recorded.
Trial Locations
- Locations (43)
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Columbia University
🇺🇸New York, New York, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Baylor Research Insitute
🇺🇸Dallas, Texas, United States
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
North Shore LIJ Health System
🇺🇸Long Island City, New York, United States
Cornell U, Weill Medical College
🇺🇸New York, New York, United States
M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
British Columbia Cancer Center
🇨🇦Vancouver, British Columbia, Canada
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
UCLA
🇺🇸Los Angeles, California, United States
University of CA San Diego
🇺🇸San Diego, California, United States
University of Missouri
🇺🇸Columbia, Missouri, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Stanford University
🇺🇸Stanford, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Yale University
🇺🇸New Haven, Connecticut, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Wake Forest University Health Services
🇺🇸Winston-Salem, North Carolina, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States