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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by A.O. Ospedale Papa Giovanni XXIII
Sponsor:
Collaborators:
Regional Hospital of Bolzano
Azienda Ospedaliera San Gerardo di Monza
Information provided by (Responsible Party):
Rambaldi Alessandro, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier:
NCT01186809
First received: August 10, 2010
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

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.

Condition Intervention Phase
Hematologic Malignancies
Biological: in vitro expanded Cytokine Induced Killer (CIK) cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)Cells After Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by A.O. Ospedale Papa Giovanni XXIII:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 39
Study Start Date: July 2009
Estimated Study Completion Date: September 2015
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cytokine Induced Killer
Sequential Infusion of Unmanipulated Donor Lymphocytes and Cytokine Induced Killer (CIK)
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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01186809

Contacts
Contact: Alessandro ar Rambaldi, Prof arambaldi@ospedaliriuniti.bergamo.it

Locations
Italy
USC Ospedali Riuniti di Bergamo, Bergamo Recruiting
Bergamo, Italy, 24128
Contact: ALESSANDRO AR RAMBALDI, PROFESSOR         
Sub-Investigator: ALESSANDRA AA ALGAROTTI, DR         
Ospedale Centrale di Bolzano Recruiting
Bolzano, Italy
Contact: SERGIO SC CORTELAZZO, DR         
Sub-Investigator: IRENE IC CAVATTONI, DR         
Ospedale San Gerardo Active, not recruiting
Monza, Italy
Sponsors and Collaborators
A.O. Ospedale Papa Giovanni XXIII
Regional Hospital of Bolzano
Azienda Ospedaliera San Gerardo di Monza
Investigators
Principal Investigator: Alessandro AR Rambaldi, Professor A.O. Ospedale Papa Giovanni XXIII
  More Information

Publications:
Responsible Party: Rambaldi Alessandro, Prof, A.O. Ospedale Papa Giovanni XXIII
ClinicalTrials.gov Identifier: NCT01186809     History of Changes
Other Study ID Numbers: Eudract number: 2008-003185-26
Study First Received: August 10, 2010
Last Updated: October 15, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by A.O. Ospedale Papa Giovanni XXIII:
hematologic malignancies (excluding Chronic Myeloid Leukemia)

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 22, 2014