Safety of Expanded Haploidentical Natural Killer Cells for Leukemia

Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia

The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.

Immunotherapy with natural killer (NK) cells may improve the results of treatment for patients with cancer. However, for better efficiency high doses of NK cells are required. For this purpose, NK cells were expanded in the presence of feeder K562 cells gene-modified for expression 4-1BBL and membrane bound IL-21. In the result of expansion, large number of activated NK cells are obtained.

Protocol of immunotherapy includes conditioning (fludarabine + cyclophosphamide or any other protocol of chemotherapy) followed by expanded NK cells intravenous infusion. To sustain proliferation of donor NK cells in vivo patients receive 6 doses of Il-2 every second day. 10 patients will be enrolled in phase I to test different doses of NK cells: 20, 50, 70, 100 and >100 x 10^6/kg.

Inclusion Criteria:

Patients:

• Relapsed acute myeloid or lymphoblastic leukemia
• Primary refractory myeloid or lymphoblastic leukemia
• Karnofsky or Lansky performance scale greater or equal to 70
• Written informed consent

Donor:

• Haploidentical family donor
• > 18 years old
• Donor suitable for cell donation and apheresis according to standard criteria
• Written informed consent

Exclusion Criteria:

Patients:

• Uncontrolled infection
• Severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age
• Positive serology for human immunodeficiency virus (HIV)

Donors:

• Pregnancy or breast feeding
• Positive serology for HIV, hepatitis B or C.