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

January 17, 2019 updated by: Rambaldi Alessandro, A.O. Ospedale Papa Giovanni XXIII

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bergamo, Italy, 24127
        • Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo) Bergamo
      • Bolzano, Italy
        • Ospedale Centrale di Bolzano
      • Monza, Italy
        • Ospedale San Gerardo

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Measures
Time Frame: Clinical response was measured at 100 days after the completion of the cell therapy program.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy Measures
Time Frame: The clinical response will be registered at day +100 after the last Cytokine Induced Killer (CIK) cell infusion
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

A.O. Ospedale Papa Giovanni XXIII

Collaborators

Regional Hospital of Bolzano
Azienda Ospedaliera San Gerardo di Monza

Investigators

  • Principal Investigator: Alessandro AR Rambaldi, Professor, Azienda Ospedaliera Papa Giovanni XXIII (Former:Ospedali Riuniti di Bergamo)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

May 15, 2017

Study Registration Dates

First Submitted

August 10, 2010

First Submitted That Met QC Criteria

August 20, 2010

First Posted (Estimate)

August 23, 2010

Study Record Updates

Last Update Posted (Actual)

January 23, 2019

Last Update Submitted That Met QC Criteria

January 17, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Eudract number: 2008-003185-26

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

final report

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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