Know Cancer

forgot password

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

Phase 2
18 Years
65 Years
Open (Enrolling)
Hematologic Malignancies

Thank you

Trial Information

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.

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.

Inclusion Criteria:

- Patients with haematologic malignancies (excluding chronic myeloid Leukemia- CML)
with a molecular, cytogenetic or haematologic relapse after allogeneic

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety Measures

Outcome Description:

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

Outcome Time Frame:

after each Cytokine Induced Killer cell infusion

Safety Issue:


Principal Investigator

Alessandro AR Rambaldi, Professor

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ospedali Riuniti di Bergamo


Italy: Ethics Committee

Study ID:

Eudract number: 2008-003185-26



Start Date:

July 2009

Completion Date:

July 2012

Related Keywords:

  • Hematologic Malignancies
  • hematologic malignancies (excluding Chronic Myeloid Leukemia)
  • Neoplasms
  • Hematologic Neoplasms