Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia
Condition: High Risk Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: CPX-351; 7+3 (cytarabine and daunorubicin)
Intervention description: 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.; 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.
Intervention MeSH terms: Cytarabine; Daunorubicin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 309.0
Sex: All
Minimum age: 60 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: AML; Acute Myeloid Leukemia; high risk AML; secondary AML; AML in elderly

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.
    

Eligibility criteria:

        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