Clinical Trial to Assess the Efficacy and Toxicity of Induction and Consolidation With CPX-351 for Patients Aged 60 to 75 Years With Secondary or High-risk Acute Myeloid Leukemia
Condition: Newly Diagnosed Secondary or High Risk AML
MeSH terms: Leukemia, Myeloid, Acute; Neoplasm Metastasis
Study type: Interventional
Phase: Phase 2

Summary: 
      This protocol corresponds to a prospective, multicentre, open label, phase II study designed
      to evaluate the efficacy of CPX-351 in elderly patients with secondary or high-risk AML. The
      clinical trial is divided into pre-treatment, treatment (induction and consolidation cycles)
      and follow-up periods and consists of a single arm group. Patients will be enrolled at
      diagnosis to follow the treatment arm. After that will start induction chemotherapy with
      CPX-351 regimen (14 days maximum screening period). Once a patient have been evaluated for
      response and recovered from major complications, he/she will start second course
      (consolidation 1), unless the bone marrow and peripheral blood assessment is showing less
      than a complete response, then a second induction may be offered. If a CR or CRi is obtained
      after the second induction course, patients will start the third course after a rest and
      recovery period. Patients aged between 60 and 65 years old are recommended to undergo an
      allo-SCT after first consolidation if they are considered fit for this procedure and they
      have a full matched related or unrelated donor. Patients aged between 65 and 70 years old can
      be proposed for an allo-SCT in CR/CRi if they have a composite HSCT co-morbidity index /age
      less than 4 and a suitable fully matched related donor. In patients over 70 years old, an
      allo-SCT in first CR should be avoided although the decision should be taken on an individual
      basis. Patients with CR/CRi who are not considered for an allo-SCT, will follow 6 maintenance
      cycles with modified courses of CPX-351 schedule. Patients showing unacceptable toxicity
      along all therapeutic phases that, in consideration of the investigator, will be prematurely
      discontinued. All patients will be followed-up for survival. The study will be analyzed on an
      intention to treat basis. Bone marrow and response assessments will be done after each
      induction and consolidation course, and every 3 months during the first 12 months after
      starting maintenance therapy. Patients will be followed-up for a minimum period of 1 year
      after the enrolment of the last patient. Additionally, after the end of the trial, patients
      will be followed-up for 2 years in order to verify survival and the evolution of the disease.
      Study design allows a maximum of 59 patients.
    

Detailed description: 
      This is a prospective, multicenter, open-label, phase II study to assess efficacy of CPX-351
      in elderly patients (60 to 75 years of age) with newly diagnosed high risk AML. The study
      includes a single arm group. The primary endpoint of the study is to assess the CR/CRi rate
      after induction with CPX-351.

      Patients will be enrolled at diagnosis to follow the treatment arm. After that they will
      start induction chemotherapy with CPX-351 regimen (14 days maximum screening period). Once a
      patient has been evaluated for response and recovered from major complications (minimum 42
      days and maximum 80 days after starting the first course), he/she will start second course
      (consolidation 1), unless the bone marrow and peripheral blood assessment is showing less
      than a partial response. If a CR or CRi is obtained after the second course, patients will
      start the third course after a rest and recovery period (minimum 42 days and maximum 80 days
      after starting the second course). After the third course an assessment of response will be
      done.

      Patients aged between 60 and 65 years old are recommended to undergo an allo-SCT after first
      consolidation if they are considered fit for this procedure and they have a full matched
      related or unrelated donor. Patients with age less than 65-70 years old can be proposed for
      an allogeneic HSCT in CR/CRi if they have a composite HSCT co-morbidity index /age less than
      4 and a suitable fully matched related donor. In patients over 70 years old, an allo-SCT in
      first CR should be avoided although the decision should be taken on an individual basis.

      Patients with CR/CRi who are not considered for an allo-SCT, will follow 6 maintenance cycles
      with modified courses of CPX-351 schedule. Patients showing unacceptable toxicity along all
      therapeutic phases that, in consideration of the investigator, will be prematurely
      discontinued. All patients will be followed-up for survival. The study will be analyzed on an
      intention to treat basis. Bone marrow and response assessments will be done after each
      induction and consolidation course, and every 3 months after starting maintenance therapy.
      Patients will be followed-up for a minimum period of 3 years after the enrollment of the last
      patient in order to know OS, disease-free, and relapse free survival (RFS), as well as on the
      duration of remission and cumulative incidence of relapse. Patients may be admitted in
      hospital to receive the experimental treatment.

      The clinical trial is divided into pre-treatment (screening), treatment periods (induction,
      consolidation and maintenance cycles) and follow-up:

      Induction cycle (1 cycle):

      It will consist of priming with daily administration of G-CSF on days -1, 1 and 2 (300
      mcg/m2/day) subcutaneously, CPX-351 day 1, 3 and 5 (100 units/m2/day) IV in 90 minutes
      infusion, and subcutaneous G-CSF from day 10 to recovery (5 mg/kg/day). The chemotherapy
      course may be administered in hospital. If a complete response is obtained after the first
      cycle of treatment, the patient will receive consolidation cycle. If a partial response is
      obtained after the first cycle of treatment, the patient will receive induction 2. Response
      to treatment will be determined by the local investigator and will be the basis for treatment
      decisions. However, if there is any doubt, it should be discussed with the Study coordinator.

      Induction 2 (1 cycle, only for patients with PR after induction 1):

      It will consist of priming with daily administration of G-CSF on days -1, 1 and 2 (300
      mcg/m2/day) subcutaneously, CPX-351 day 1 and 3 (100 units/m2/day) IV in 90 minutes infusion,
      and subcutaneous G-CSF from day 10 to recovery (5 mg/kg/day). The chemotherapy course may be
      administered in hospital.

      Consolidation cycle (up to 2 cycles):

      It will consist of priming with daily administration of G-CSF on days -1, 1 and 2 (300
      mcg/m2/day) subcutaneously, CPX-351 day 1 and 3 (65 units/m2/day) IV in 90 minutes infusion,
      and subcutaneous G-CSF from day 10 to recovery (5 mg/kg/day). The chemotherapy course may be
      administered in hospital. Patients aged between 60 and 65 years old are recommended to
      undergo an allo-SCT after first consolidation if they are considered fit for this procedure
      and they have a full matched related or unrelated donor. Patients with age between 65-70
      years old can be proposed for an allogeneic HSCT in CR/CRi if they have a composite HSCT
      co-morbidity index /age less than 4 and a suitable fully matched related donor. In patients
      over 70 years old, an allo-SCT in first CR should be avoided although the decision should be
      taken on an individual basis.

      Maintenance cycle (up to 6 cycles):

      For patients in CR and when an allo-SCT is not feasible or recommended, a maintenance
      treatment could be started for up to 6 additional cycles, on every 4 to 8 weeks courses,
      according to hematologic recovery.

      It will consist of CPX-351 day 1 (50 units/m2/day) IV in 90 minutes infusion. Subcutaneous
      G-CSF may be used to recovery (5 mg/kg/day) in patients with grade 4 neutropenia and
      confirmed CR.
    

Intervention name(s): CPX-351
Intervention type(s): Drug
Intervention description(s): CPX-351 has IV administration Vyxeos contains 2.2 mg/mL and 5 mg/mL powder for concentrate for solution for infusion of Daunorubicin and cytarabine.
Each vial contains 44 mg of daunorubicin and 100 mg of cytarabine. After reconstitution, the solution contains 2.2 mg/mL daunorubicin and 5 mg/mL cytarabine
Intervention model: Single Group Assignment
Intervention model description: This protocol corresponds to a prospective, multicenter, open-label, phase II study to assess efficacy of CPX-351 in elderly patients (60 to 75 years of age) with newly diagnosed high risk AML. In the context of this protocol, a treatment cycle is defined as the first day of study drug administration (Day 1) up to and including the day before the first day of the treatment cycle immediately afterwards. The treatment cycles will begin after Day 42 but no later than Day 80, counting from Day 1 of the treatment cycle immediately before.
Treatment cycles may be administered while the patient is hospitalized. Patients will receive a maximum of 4 treatment cycles (up to 2 inductions and 2 consolidations) and 6 maintenance cycles. Clinical conditions in the care of patients with acute leukemia require the need for flexibility. However, deviations from the study treatment defined in this section must be prospectively discussed with the coordinator.
Masking: None (Open Label)
Primary purpose: Other
Keywords: Secondary AML; High risk AML