Clinical trial NCT00394381: Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome
Official title: Autologous Cytokine-induced Killer Cell Adoptive Immunotherapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome, High Grade
Keywords: acute myeloid leukemia
myelodysplastic syndrome
autologous CIK cells
autologous peripheral blood stem cell transplant
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
Collaborators: name: National Medical Research Council (NMRC), Singapore
First posted: 2006-11-01
Enrollment: 17
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase I/II study to explore the feasibility and efficacy of autologous CIK cells in patients with acute myeloid leukemia (AML)/ high grade myelodysplastic syndrome (MDS)

1. Group 1: As adjuvant therapy in minimal residual disease state after autologous PBSCT.
2. Group 2: As an adoptive immunotherapy in untreated disease state when conventional therapy with curative intent is not applicable

Detailed description: This is a Phase I /II study on the feasibility / efficacy of adoptive immunotherapy with autologous CIK cells for the following 2 groups of patients who have AML or high grade MDS :

1. Group 1 patients in minimal residual disease state post autologous peripheral blood stem cell transplant ( PBSCT ), and
2. Group 2 patients with untreated high grade MDS or AML, who are not fit for standard curative intent chemotherapy.

The CIK cells will be generated by leukapheresis from patients and cultured in GMP facilities. Four repeated infusions will be given for a target dose of 1x10e10 T cell per infusion.

Efficacy will be assessed by

1. Disease free survival compared to historical control in group 1 given CIK cells post autologous PBSCT as adjuvant immunotherapy (n=20 over 3 years), and
2. Effect on the peripheral or marrow leukemia cell load in group 2 patients given CIK cells as alternative therapy in place of chemotherapy (n=10).

Eligibility criteria: Inclusion Criteria:

1. For Group 1: AML or MDS post autologous peripheral blood or marrow stem cell transplant.
2. For Group 2: High grade MDS ( RAEB or RAEBIT ) or AML, whom the haematologist in charge has assessed and deemed unfit for chemotherapy with curative intent.Patients must have fairly stable white cell count requiring only low dose or no myelosuppressive medication
3. Patients must understand the trial nature of this treatment and accept the possible absence of benefit.

Exclusion Criteria:

1. uncontrolled infection
2. life expectancy less than 6 weeks.
3. Contraindication to undergo one session of leukapheresis for PBMNC harvesting

Primary outcomes:
measure: blood count changes
timeFrame: three months
measure: T lymphocyte subsets
timeFrame: three months
measure: T cell functions
timeFrame: 3 months
measure: adverse reactions
timeFrame: 24 hour
Secondary outcomes:
measure: relapse rate
timeFrame: 5 year
measure: survival
timeFrame: 5 year
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Singapore General Hospital
name: Yeh-Ching Linn, MBBS, MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Linn YC, Lau LC, Hui KM. Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br J Haematol. 2002 Jan;116(1):78-86. doi: 10.1046/j.1365-2141.2002.03247.x.
citation: Leemhuis T, Wells S, Scheffold C, Edinger M, Negrin RS. A phase I trial of autologous cytokine-induced killer cells for the treatment of relapsed Hodgkin disease and non-Hodgkin lymphoma. Biol Blood Marrow Transplant. 2005 Mar;11(3):181-7. doi: 10.1016/j.bbmt.2004.11.019.
citation: Schmidt-Wolf IG, Finke S, Trojaneck B, Denkena A, Lefterova P, Schwella N, Heuft HG, Prange G, Korte M, Takeya M, Dorbic T, Neubauer A, Wittig B, Huhn D. Phase I clinical study applying autologous immunological effector cells transfected with the interleukin-2 gene in patients with metastatic renal cancer, colorectal cancer and lymphoma. Br J Cancer. 1999 Nov;81(6):1009-16. doi: 10.1038/sj.bjc.6690800.
citation: Jiang H, Liu KY, Tong CR, Jiang B, Lu DP. [The efficacy of chemotherapy in combination with auto-cytokine-induced killer cells in acute leukemia]. Zhonghua Nei Ke Za Zhi. 2005 Mar;44(3):198-201. Chinese.