Autologous Cytokine Induced Killer Cells (CIK) for Chronic Myeloid Leukemia (CML) Patients on Standard Drug Therapy
Condition: Chronic Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an extension of our ongoing clinical trial using ex vivo expanded autologous
      Cytokine-induced killer (CIK) cells as an adoptive cellular immunotherapy for haematological
      malignancies. The pre-existing clinical trial targets patient with acute myeloid leukemia or
      MDS, and relapsed disease post allogeneic transplant.

      Chronic myeloid leukemia (CML) is a disease with good response to kinase inhibitors. There
      are however patients in transformed phase of the disease who do not respond to these
      treatment. A small proportion of patients with response to Imatinib may develop mutations
      resulting in drug resistance. In addition, the vast majority of patients with a good response
      to the kinase inhibitors still have persistent CML cells detectable at a molecular level. It
      is known that the CML progenitors are not sensitive to the kinase inhibitors. On the other
      hand, immune mediated mechanism is known to be able to eradicate CML as shown by efficacy of
      donor lymphocyte infusion in the allogeneic transplant setting. Early clinical trials have
      shown clearance of bcr-abl using peptide vaccination. There is also convincing mouse data
      showing eradication of CML at molecular level by autologous CIK cells, but no clinical trial
      has been done using CIK cells for CML.

      We therefore plan to expand our current CIK trial to include CML as a disease, for CML
      patients with various degree of response to the kinase inhibitors which have already offered
      its maximal effect. We aim to study whether autologous CIK cells may further improve disease
      response, either in the eradiation of minimal residual disease, or in conjunction with
      chemotherapy for control of high tumour load disease.
    

Detailed description: 
      Patients with CML falls into various groups based on their disease stage and response to
      kinase inhibitors. In the context of currently available kinase inhibitors, allogeneic
      transplant and the various available new drug trials, there are still some patients who will
      not achieve a satisfactory or sustainable response. For such patients, we aim to employ CIK
      cell as an immunotherapeutic modality concurrent with their original CML-specific therapy.
      This will enable us to explore any additional activity of CIK cells against CML without any
      compromise to their ongoing, established treatment.

      The following groups of patients are potential candidates:

        1. Blast crisis / accelerated phase patients who have failed to response to the kinase
           inhibitors but are fit to undergo induction chemotherapy as for the acute leukemia.
           Repeated cycles of CIK will be given in phase with the planned chemotherapy cycles, to
           observe for achievement of any remission and its durability.

        2. Blast crisis / accelerated phase patients who have achieved a haematological or
           cytogenetic response to the kinase inhibitors, but do not have further definitive
           curative options eg allogeneic transplant. In the absence of long term data with
           Dasatinib or Nilotinib , it is justifiable to study the efficacy of addition of CIK
           therapy to their baseline best response achievable with drug therapy.

        3. Patients with resistance to the currently available kinase inhibitors due to T315I
           mutation or other undefined mutations, with progressive relapse either at molecular,
           cytogenetic or haematological level, and do not have transplant as a curative option. In
           this group of patients additional of CIK to current treatment will show any activity of
           CIK against the drug-resistant mutant CML cells.

        4. Patients who have achieved a stable but residual molecular evidence of CML, who are
           willing to explore additional means with a hope to eradication of MRD. Since the role of
           immunotherapy is most relevant in MRD, CIK infusion will provide the proof of principal
           observation of whether imatinib-resistant CML Philadelphia stem cells can be eradicated
           by these ex vivo activated and expanded cytotoxic T cells.
    

Intervention name(s): Autologous CIK cell infusion
Intervention type(s): Biological
Intervention description(s): 4 CIK cells will be infused into patients at regular 3-weekly intervals for 4 infusions. The target cell dose per infusion is 1x10e10 CD3 cells. For patients with uncontrolled accelerated or blastic transformation undergoing chemotherapy, this will be given at the nadir of lymphopenia following chemotherapy. For other patients this will be given without interruption of the ongoing treatment with Imatinib or other kinase inhibitor.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: chronic myeloid leukemia; autologous cytokine induced killer cells; Chronic myeloid leukemia in blast crisis treated with chemotherapy or kinase inhibitors; Chronic myeloid leukemia with mutation resistant to kinase inhibitors; chronic myeloid leukemia with good response to kinase inhibitor and stable persistence of residual disease