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

This study is currently recruiting participants.
Verified May 2012 by Singapore General Hospital
Sponsor:
Collaborator:
National Medical Research Council (NMRC), Singapore
Information provided by (Responsible Party):
Linn Yeh Ching, Singapore General Hospital
ClinicalTrials.gov Identifier:
NCT00460694
First received: April 12, 2007
Last updated: May 14, 2012
Last verified: May 2012
  Purpose

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 Intervention 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

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: A Phase II Trial on Allogeneic Cytokine-induced Killer Cell Immunotherapy for Relapse After Allogeneic Marrow Transplant for Haematological Malignancies

Resource links provided by NLM:


Further study details as provided by Singapore General Hospital:

Primary Outcome Measures:
  • Feasibility of expansion of frozen donor mononuclear cells into CIK [ Time Frame: 2 year ] [ Designated as safety issue: No ]
  • Toxicity including GVHD and marrow aplasia [ Time Frame: 1 year from infusion for each patient ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Efficacy in terms of disease response as compared to previous treatment modality ie unmanipulated DLI [ Time Frame: 2 years from infusion for each patient ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: August 2006
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: infusion of allogeneic CIK cells
    infusion of allogeneic CIK cells at graded doses
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   12 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00460694

Contacts
Contact: Yeh-Ching Linn, MBBS, MRCP (65) 62223322 ext 6608 linn.yeh.ching@sgh.com.sg
Contact: Mickey Koh, MBBS (S'pore),MRCP (UK), PhD (65) 62130602 mickey_koh@hsa.gov.sg

Locations
Singapore
Singapore General Hospital Recruiting
Singapore, Singapore, 169608
Contact: Yeh-Ching Linn, MBBS, MRCP    (65) 62223322 ext 6608    linn.yeh.ching@sgh.com.sg   
Contact: Mickey Koh, MBBS, MRCP, PhD    (65) 62130602    Mickey_koh@hsa.gov.sg   
Sub-Investigator: Yeow Tee Goh, MBBS(S'pore), MRCP(UK)         
Sub-Investigator: William Hwang, MBBS, MRCP, M Med         
Sponsors and Collaborators
Singapore General Hospital
National Medical Research Council (NMRC), Singapore
Investigators
Principal Investigator: Yeh-Ching Linn, MBBS, MRCP Singapore General Hospital
  More Information

Publications:
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: Linn Yeh Ching, dr, Singapore General Hospital
ClinicalTrials.gov Identifier: NCT00460694     History of Changes
Other Study ID Numbers: CIK#2/2007, NMRC/1097/2006
Study First Received: April 12, 2007
Last Updated: May 14, 2012
Health Authority: Singapore: Health Sciences Authority

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

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

ClinicalTrials.gov processed this record on April 17, 2014