Autologous Cytokine Induced Killer Cells (CIK) for Chronic Myeloid Leukemia (CML) Patients on Standard Drug Therapy

NCT ID: NCT00815321

Last Updated: 2017-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2011-11-30

Brief 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.

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Autologous CIK cell infusion

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 Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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.

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

3. Patients with resistance to genetic or haematological level, and do not have transplant as a curative option.

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.

Patients must understand the trial nature of this study and the additional leukapheresis procedure needed for harvesting mononuclear cells.

Exclusion Criteria

On recruitment :

1. Renal impairment with Cr >200mmol/uL

2. Liver impairment with transaminase >5x upper limit which is not due to disease

3. Limited life expectancy <3 months

On day of infusion

1. uncontrolled infection or significant bleeding

2. unstable vital signs

3. any degree of hypoxia requiring oxygen therapy.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Singapore General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yeh Ching Linn, MBBS, MRCP

Role: PRINCIPAL_INVESTIGATOR

Singapore General Hospital

Locations

Dept of Haematology, Singapore General Hospital

Singapore, , Singapore

Countries

Singapore

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Other Identifiers

CIK#3/2008

Identifier Type: -

Identifier Source: org_study_id