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

NCT03027102 | Completed Phase 1

• 1 other identifier: OZM-079
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine the safety and toxicity of incremental doses of Double Negative T (DNT) cells in human subjects with high risk acute myeloid leukemia (AML). DNT cells are mature T lymphocytes that comprise \~1% of white blood cells in humans. Injection of DNTs from healthy donors has been demonstrated to be effective against AML cells. DNT cells will be collected from healthy volunteers and injected into patients.

Conditions

Acute Myeloid Leukemia

Keywords

allogenic double negative T cells; DNT cells

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events and abnormal laboratory studies.

  Patients will be assessed for adverse events based upon, but not limited to, monitoring of vital signs and prescribed laboratory studies. Adverse events (AE) will use the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE). This study will utilize the CTCAE Version 4.03 for adverse event reporting.

  2 years

Secondary Outcomes (2)

• Number of cells with disease specific mutations per patient

  2 years

• Leukemia load

  2 years

Study Arms (2)

Patient Arm

EXPERIMENTAL

Patients will receive DNT cells from healthy donors.

Biological: DNT cells

Donor Arm

NO INTERVENTION

Healthy volunteer donors will donate blood.

Interventions

DNT cells BIOLOGICAL

DNT cells will be expanded (increased in numbers) in the laboratory, in order to enhance their tumour destroying potential before infusion into AML patients.

Patient Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Ozmosis Research Inc.: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G2M9, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 20, 2017
• Study Start: August 15, 2017
• Primary Completion: December 10, 2024
• Study Completion: December 10, 2024
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

CA (1)