Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)Cells After Allogeneic Stem Cell Transplantation
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.
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
after each Cytokine Induced Killer cell infusion
Alessandro AR Rambaldi, Professor
Ospedali Riuniti di Bergamo
Italy: Ethics Committee
Eudract number: 2008-003185-26