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
- 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
- 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,
- 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