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

NCT00460694 | Completed Phase 1 DMC

• 2 other identifiers: CIK#2/2007NMRC/1097/2006
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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 .

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Chronic Myeloid Leukemia; Non Hodgkin's Lymphoma; Hodgkin's Disease; Myelodysplastic Syndrome; Multiple Myeloma

Keywords

allogeneic transplant; haematological malignancies; allogeneic CIK cells

Outcome Measures

Primary Outcomes (2)

• Feasibility of expansion of frozen donor mononuclear cells into CIK

  2 year

• Toxicity including GVHD and marrow aplasia

  1 year from infusion for each patient

Secondary Outcomes (1)

• Efficacy in terms of disease response as compared to previous treatment modality ie unmanipulated DLI

  2 years from infusion for each patient

Interventions

infusion of allogeneic CIK cells BIOLOGICAL

infusion of allogeneic CIK cells at graded doses

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• This trial includes only patients who have relapsed after an allogeneic transplant, who have either:
• No response to conventional DLI given for at least one dose, or
• 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
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Singapore General Hospital: lead
• National Medical Research Council (NMRC), Singapore: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, 169608, Singapore

Location

Related Publications (1)

• 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

  BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Non-Hodgkin; Hodgkin Disease; Myelodysplastic Syndromes; Multiple Myeloma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Study Officials

• Yeh-Ching Linn, MBBS, MRCP

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2007
• First Posted: April 16, 2007
• Study Start: August 1, 2006
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 10, 2017

Record last verified: 2017-02

Locations

SG (1)