Cytokine Induced Killer (CIK) Cells In Leukemia Patients

Hematologic Malignancies Clinical Trial

— CIK2  

Official title:

Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)Cells After Allogeneic Stem Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01186809
• Other study ID #: Eudract number: 2008-003185-26
• Status: Completed
• Phase: Phase 2
• Start date: July 2009
• Est. completion date: May 15, 2017

Study information

• Verified date: January 2019
• Source: A.O. Ospedale Papa Giovanni XXIII
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: May 15, 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Malignancies
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo) Bergamo	Bergamo
Italy	Ospedale Centrale di Bolzano	Bolzano
Italy	Ospedale San Gerardo	Monza

Sponsors (3)

Lead Sponsor	Collaborator
A.O. Ospedale Papa Giovanni XXIII	Azienda Ospedaliera San Gerardo di Monza, Regional Hospital of Bolzano

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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 — View 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-ind — View 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. — View Citation

Introna M, Pievani A, Borleri G, Capelli C, Algarotti A, Micò 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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Measures	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	Clinical response was measured at 100 days after the completion of the cell therapy program.
Secondary	Efficacy Measures	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	The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion