Cytokine Induced Killer (CIK) Cells In Leukemia Patients (CIK2)

• Safety Measures [ Time Frame: after each Cytokine Induced Killer cell infusion ] [ Designated as safety issue: Yes ]
  The occurrence of a grade 4 acute graft versus host disease (GVHD), judged to be related to the study medication. Grading and staging will be performed using the Glucksberg scale
  
  

• Efficacy Measures [ Time Frame: The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion ] [ Designated as safety issue: No ]
  The proportion of patients achieving a complete, a partial or a hematologic improvement in responses to the experimental infusion of cytokine induced killer (CIK)cells
  
  

Biological: in vitro expanded Cytokine Induced Killer (CIK) cells
Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). Cytokine Induced Killer administrations will be separated by 3 weeks intervals
Other Names:
• patients will be offered Cytokine Induced Killer(CIK) cells.
• Four combinations of escalating Cytokine Induced Killer (CIK) cells infusions will be provided, until the MTD will be defined.
• Combination 1st CIK cells infusion 2nd CIK cells infusion 3rd CIK cells infusion
• 1 1x106/Kg 1x106/Kg 5x106/kg
• 2 1x106/Kg 5x106/kg 5x106/kg
• 3 1x106/Kg 5x106/kg 10x106/kg
• 4 5x106/kg 5x106/kg 10x106/kg

This study is an open-label, multicenter, exploratory phase IIA study to evaluate the safety (dose-finding) and efficacy of a sequential administration of donor derived unmanipulated DLI and in vitro expanded Cytokine Induced Killer(CIK) cells.

Two infusions of unmanipulated donor lymphocytes (1x106/Kg each) will be given with a minimum interval of 3 weeks. Three infusions of donor Cytokine Induced Killer (CIK) cells will be administered according to a dose escalating program, starting 3 weeks after second Donor Lymphocyte Infusions (DLI). In presence of grade 2 or more acute graft versus host disease(GVHD), the patient will not receive the next scheduled infusion. Only grade 4 acute graft versus host disease (aGVHD) is considered for the dose limiting toxicity (DLT). Once identified the maximally tolerated dose (MTD), this same combination of doses will be administered up to 24 patients in a two-stage minimax design.

Primary Endpoints

The primary endpoints of the Phase IIA study are:

1. the Maximally Tolerated Dose (MTD) - (safety end-point)
2. the cumulative incidence of molecular, karyotypic or haematologic responses at day +100 after the end of the cell therapy program - (efficacy end-point)

Secondary Endpoints Progression Free Survival (PFS) Progression Free Survival (PFS) will be defined as any evidence of molecular, cytogenetic or haematologic disease progression. Cytogenetic and/or molecular relapse will be defined where available as any evidence of a pre-transplant defined abnormality using conventional cytogenetics or FISH techniques or molecular probes. Assessments will be performed at 1 year after the end of the cell therapy program Overall Survival (OS) The Overall Survival(OS) will be assessed by 1 year after the end of the cell therapy program. For assessment of the Overall Survival (OS), events will be deaths for any causes, patients being censored if alive.