Allogeneic Cytokine-induced Killer Immunotherapy for Relapse After Allogeneic Marrow Transplant for Haematological Malignancies (alloCIK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00460694
Recruitment Status : Completed
First Posted : April 16, 2007
Last Update Posted : February 10, 2017
National Medical Research Council (NMRC), Singapore
Information provided by (Responsible Party):
Singapore General Hospital

Brief Summary:

Cytokine-induced killer ( CIK ) cells have been shown by our lab to be cytolytic against both autologous and allogeneic acute myeloid leukemia ( AML ) cells. Large scale expansion of CIK cells has also been shown to be feasible in healthy allogeneic stem cell donors as well as in patients undergoing mobilization for autologous transplant.

Donor lymphocyte infusion (DLI) has been shown to be active against some haematological malignancies including CML, AML, MDS,NHL and Hodgkin's disease. These donor lymphocytes can be further activated in vitro to become CIK cells. At least 2 other centers in the world have given allogeneic CIK cells for patients relapsing post allogeneic transplant for a variety of haematological malignancies. These early reports have demonstrated feasibility, absence of increased GVHD and possible efficacy in some cases.

We are proposing a Phase I /II study on the feasibility / efficacy of immunotherapy with allogeneic CIK cells for patients who relapse after allogeneic marrow transplant for their haematological malignancies. These patients have to be either refractory to conventional donor lymphocyte infusion, or need a larger number of donor lymphocyte than could be provided by unmanipulated donor lymphocytes. Donor lymphocytes will be collected and cultured in GMP facilities to maturity, then infused into patients. This will be given in graded doses at 4 weekly intervals and continued on in the absence of GVHD till remission is achieved or disease progression occurs. Patients may receive various forms of chemotherapy appropriate to the clinical condition in each case before the allogeneic CIK infusion.

Efficacy will be assessed by comparing the response to allogeneic CIK infusion vs that to due to conventional DLI, ie response to the two different treatment using DLI response as the comparator. We expect about 10 such cases to be done over the next 3 years. Significant statistics is unlikely to be generated but observation and description of the response can generate useful information for presence or not of the efficacy of such a treatment.

If clinical efficacy and superiority over conventional DLI is demonstrated, then future allogeneic CIK may take the place of DLI in this group of poor prognosis patients who relapse after allogeneic transplant .

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Non Hodgkin's Lymphoma Hodgkin's Disease Myelodysplastic Syndrome Multiple Myeloma Biological: infusion of allogeneic CIK cells Phase 1 Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial on Allogeneic Cytokine-induced Killer Cell Immunotherapy for Relapse After Allogeneic Marrow Transplant for Haematological Malignancies
Study Start Date : August 2006
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Intervention Details:
    Biological: infusion of allogeneic CIK cells
    infusion of allogeneic CIK cells at graded doses

Primary Outcome Measures :
  1. Feasibility of expansion of frozen donor mononuclear cells into CIK [ Time Frame: 2 year ]
  2. Toxicity including GVHD and marrow aplasia [ Time Frame: 1 year from infusion for each patient ]

Secondary Outcome Measures :
  1. Efficacy in terms of disease response as compared to previous treatment modality ie unmanipulated DLI [ Time Frame: 2 years from infusion for each patient ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   12 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

This trial includes only patients who have relapsed after an allogeneic transplant, who have either:

  1. No response to conventional DLI given for at least one dose, or
  2. No possibility of access to large number of donor lymphocyte for repeated doses of DLI, This applies to cases of unrelated transplant or cord blood transplant
  3. Patients who developed significant GVHD to conventional DLI, but had no other therapeutic option. In such cases the rationale is based on mice studies of mismatched CIK producing much less GVHD than mismatched unmanipulated splenocytes.

In view of the period taken to culture the cell to maturity, patient must have a life expectancy of more than one month. Interim measures eg chemotherapy or conventional DLI will be given during the interval so that ongoing treatment will not be compromised in any way.

Exclusion Criteria:

  1. Uncontrolled infection or significant bleeding
  2. Unstable vital signs
  3. Any degree of hypoxia requiring oxygen therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00460694

Singapore General Hospital
Singapore, Singapore, 169608
Sponsors and Collaborators
Singapore General Hospital
National Medical Research Council (NMRC), Singapore
Principal Investigator: Yeh-Ching Linn, MBBS, MRCP Singapore General Hospital

1. YC Linn, LC Lau, KM Hui Generation of cytokine-induced killer cells from leukemic samples with in vitro cytotoxicity against autologous and allogeneic leukemic blasts British Journal of Haematology, 2002, 116: 78-86 2. C Sheffold, M Edinger, R S Negrin A Phase I trial of autologous cytokine-indueced killer cells for transplant of relapsed Hodgkin's disease and Non Hodgkin's lymphoma Biol of Blood and Marrow Transplant 2005, 11:181-187 3. Hao Jiang, Kaiyan Liu, Chunrong Tong, Bin Jiang, Daopei Lu The efficacy of chemotherapy in combination with autologous cytokine-induced killer cellsi n acute leukemia Chinese J Internal Med 2005, 44(3): 198-201 4. Jeanette Baker, Michael R Vernais, Maki Ito et al Expansion of cytolytic CD8+ natural killer T cells with limited capacity for graft-versus- host disease induction due to interferon gamma productin Blood, 2001, 97(!)(: 2923-2931 5. Ginna G Laport, Kevin Sheehan, Robert Lowsky et al Cytokine Induced Killer (CIK) cells as post transplant immunotherapy following allogeneic haemopoietic cell transplantation (Oral session ) Blood 2006, 108 (11) #412 6.Martino Introna, Gianmaria Borleri, Elena Conti et al Infusion of donor derived Cytokine-induced Killer Cells may induce clinical remission with limited GVHD in patients relapsing after allogeneic stem cell transplantation ( poster session) Blood 2006, 108(11), #3698 7. David L Porter, Bruce L Levine, Nancy Bunin et al A phase I trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation Blood 2006, 107 (4), 1325-1331

Responsible Party: Singapore General Hospital Identifier: NCT00460694     History of Changes
Other Study ID Numbers: CIK#2/2007
First Posted: April 16, 2007    Key Record Dates
Last Update Posted: February 10, 2017
Last Verified: February 2017

Keywords provided by Singapore General Hospital:
allogeneic transplant
haematological malignancies
allogeneic CIK cells

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Multiple Myeloma
Myelodysplastic Syndromes
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hodgkin Disease
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Myeloproliferative Disorders