Study of Allogeneic Double Negative T Cells (DNT-UHN-1) in Patients With High Risk Acute Myeloid Leukemia

Patient Inclusion Criteria:

• Patients with AML who are 18 years of age or older.
• Viably frozen cells from the time of diagnosis or relapse are available for sensitivity testing to DNT cells.
• Patients have given informed consent.
• Patients in remission following FLAG-Ida induction therapy who are receiving consolidation treatment.
• Creatinine < 1.5 x ULN within 7 days prior to day 1 of study treatment.
• AST, ALP, bilirubin < 1.5x ULN within 7 days prior to day 1 of study treatment.
• Female patients of childbearing potential should be willing to use 2 methods of birth control (Refer to section 9.2.15 or be surgically sterile, or abstain from heterosexual activity for the course of the study from day 1 until 1 months following chemotherapy. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 2 years.

Male patients should use condoms or abstain from sex from the time of beginning chemotherapy to 1 month after the chemotherapy.

• Patients must be able to comply with study procedures, at the minimum, until all DNT-UHN-1 cells are out of their system.

Patient Exclusion Criteria:

• ECOG performance status <2.
• Patients with a known persistent infection.
• Patients with known active CNS disease.
• Life expectancy < 3 months.
• Patients should be off Cox2 inhibitors and corticosteroids for at least 3 days prior to and 7 days after infusion of DNT cells.
• Patients who are HIV positive.
• Patients for whom healthy donor DNT kill <10% of patient's blast cells.

Donor Inclusion Criteria:

• Has given written informed consent.
• Is 18 years of age or older.
• No known prior blood product transfusion or surgery.
• Blood electrolytes (Sodium, Potassium, Chloride, Bicarbonate, Magnesium, Phosphate, Calcium) within normal ranges.
• Normal complete blood counts.
• Normal liver and kidney function (Bilirubin, AST, ALT, ALP, LDH, plasma albumin, creatinine).
• Negative for transfusion transmissible illnesses (CMV, HIV I/II, HTLV I/II, Hepatitis B Surface Antigen, Hepatitis B Surface Antibody, Hepatitis B Core Antibody, Hepatitis C Antibody) within 30 days of blood collection for DNT cell expansion for patient infusion.
• Negative for evidence of exposure to West Nile Virus, Syphilis within 30 days of blood collection for DNT cell expansion for patient infusion.
• DNT cell expansion yield is >108 per mL blood using the standard protocol. Expanded DNT cells show ≥20% cytotoxicity to at least 3 AML cell lines (MV4-11 AML3, and U937).
• The donor who meet all donor inclusion/exclusion criteria, whose DNT cells show the most potent killing (minimum >10% killing) of AML patient's blast cells (blast cells frozen at time of diagnosis or relapse) will be approached for participation in this study.

Donor Exclusion Criteria:

• With a history of high risk behavior including, but not limited to, a history of piercing (except ear lobes), tattoos or other body modification.
• Has serious illnesses such as cardiovascular disease & cancer.
• Has sexually transmissible disease.
• Has history of intravenous drug use.
• Persons who received any vaccinations in past 3 months prior to enrolment into this study.
• Persons who travel outside the U.S. and Canada in the past 3 years prior to enrolment into this study, to areas that are considered endemic for malaria.
• Persons who have received blood components or other human tissues in the past 12 months prior to enrolment into this study (however this may be reduced to 6 months if nucleic acid testing (NAT) is used for the tests).
• Pregnant or lactating.
• Persons at risk of transmitting a hematological or immunological disease.
• Persons with transmissible genetic diseases in the family.
• On prescription medication.
• Persons with prion-related disease.
• Persons with a neurological disease of an unestablished etiology.
• Persons with active encephalitis or meningitis of infectious or unknown etiology.
• Persons with rabies or persons who, within the past 6 months, were bitten by an animal and treated as if the animal was rabid.
• Persons with a family history of Creutzfeldt-Jakob disease.
• Persons who have received human-derived pituitary growth hormone or dura mata.
• Persons who have known or suspected sepsis at the time of donation.