Clinical trial NCT01186809: Cytokine Induced Killer (CIK) Cells In Leukemia Patients
Official title: Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)Cells After Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematologic Malignancies
Keywords: hematologic malignancies (excluding Chronic Myeloid Leukemia)
Lead sponsor: A.O. Ospedale Papa Giovanni XXIII
Sponsor class: OTHER
Collaborators: name: Regional Hospital of Bolzano
name: Azienda Ospedaliera San Gerardo di Monza
First posted: 2010-08-23
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients with haematologic malignancies (excluding chronic myeloid Leukemia- CML) with a molecular, cytogenetic or haematologic relapse after allogeneic transplantation.
* Patients with an available donor willing to donate peripheral blood lymphocytes
* Immunosuppression must be withdrawn at the beginning of the cell therapy program
* Written informed consent prior to any study procedures being performed

Exclusion Criteria:

* Donors positive for HIV, HBV or HCV, or unfit to undergo leukapheresis
* Patients with active acute or chronic Graft versus host disease (GvHD)
* Patients with rapidly progressive disease or not controlled by palliative supportive treatments including chemotherapy and with a life expectancy less than 8 weeks
* Patients with severe psychiatric illness or any disorder that compromises ability to give truly informed consent for participation in this study

Primary outcomes:
measure: Safety Measures
timeFrame: Clinical response was measured at 100 days after the completion of the cell therapy program.
Secondary outcomes:
measure: Efficacy Measures
timeFrame: The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo) Bergamo
city: Bolzano
country: Italy
facility: Ospedale Centrale di Bolzano
city: Monza
country: Italy
facility: Ospedale San Gerardo
Study officials:
affiliation: Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo)
name: Alessandro AR Rambaldi, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Introna M, Franceschetti M, Ciocca A, Borleri G, Conti E, Golay J, Rambaldi A. Rapid and massive expansion of cord blood-derived cytokine-induced killer cells: an innovative proposal for the treatment of leukemia relapse after cord blood transplantation. Bone Marrow Transplant. 2006 Nov;38(9):621-7. doi: 10.1038/sj.bmt.1705503. Epub 2006 Sep 18.
citation: Introna M, Borleri G, Conti E, Franceschetti M, Barbui AM, Broady R, Dander E, Gaipa G, D'Amico G, Biagi E, Parma M, Pogliani EM, Spinelli O, Baronciani D, Grassi A, Golay J, Barbui T, Biondi A, Rambaldi A. Repeated infusions of donor-derived cytokine-induced killer cells in patients relapsing after allogeneic stem cell transplantation: a phase I study. Haematologica. 2007 Jul;92(7):952-9. doi: 10.3324/haematol.11132.
citation: Capelli C, Salvade A, Pedrini O, Barbui V, Gotti E, Borleri G, Cabiati B, Belotti D, Perseghin P, Bellavita P, Biondi A, Biagi E, Rambaldi A, Golay J, Introna M. The washouts of discarded bone marrow collection bags and filters are a very abundant source of hMSCs. Cytotherapy. 2009;11(4):403-13. doi: 10.1080/14653240902960437.
citation: Introna M, Pievani A, Borleri G, Capelli C, Algarotti A, Mico C, Grassi A, Oldani E, Golay J, Rambaldi A. Feasibility and safety of adoptive immunotherapy with CIK cells after cord blood transplantation. Biol Blood Marrow Transplant. 2010 Nov;16(11):1603-7. doi: 10.1016/j.bbmt.2010.05.015. Epub 2010 Jun 1.