Cytokine Induced Killer (CIK) Cells In Leukemia Patients
Condition: Hematologic Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of the Phase IIA study are to:

        1. define the safety profile

        2. evaluate the efficacy of a sequential infusion of unmanipulated Donor Lymphocyte
           Infusions (DLI) and Cytokine Induced Killer (CIK) cells for the treatment of molecular,
           cytogenetic or hematologic relapse after hematopoietic stem cell transplantation and The
           progression free survival and the overall survival after the sequential infusion of
           Donor Lymphocyte Infusions (DLI) and Cytokine Induced Killer(CIK) cells.
    

Detailed description: 
      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.
    

Intervention name(s): in vitro expanded Cytokine Induced Killer (CIK) cells
Intervention type(s): Biological
Intervention description(s): 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 intervention name(s): 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
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hematologic malignancies (excluding Chronic Myeloid Leukemia)