Newly Diagnosed Secondary or High Risk AML Clinical Trial
Official title:
A Phase II, Multicentre, Open Label 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
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.
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. ;