Clinical trial NCT04008381: Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia
Official title: Efficacy and Safety of Ex-vivo Expanded γδ T Lymphocytes in Patients With Refractory/Relapsed Acute Myeloid Leukaemia: a Single-center, Open-label, Single-arm Clinical Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: gamma-delta T
Refractory/Relapsed
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
Collaborators: name: Jinan University, China
First posted: 2019-07-05
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study investigates the potential curative properties of ex-vivo expanded gamma delta T-cells obtained from a blood-related donor for patients with relapsed or refractory acute myeloid leukemia.

Detailed description: This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of ex-vivo expanded γδ T-lymphocytes in patients with relapsed or refractory acute myeloid leukemia. PBMCs will be separated from peripheral blood of suitable donors. After making them potential cancer killer γδ T Cells, they will be infused to the patients as an immunotherapy treatment.

Eligibility criteria: Inclusion Criteria:

1. History of acute myeloid leukaemia (initially diagnosed by presence of 20% or more blast cells with myeloid or monocytic differentiation confirmed by flow cytometry in peripheral blood or bone marrow)
2. Relapsed or refractory AML. A. AML relapse after intensive chemotherapy; B. AML relapse after allogeneic HCT; C. AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or decitabine); D. No response to at least 4 cycles of low intensity therapy; E. AML refractory to 2 cycles of induction chemotherapy.
3. Presence of \> 5% of blasts in bone marrow or peripheral blood smear
4. Patient not eligible for or does not consent to high dose salvage chemotherapy and/or allogeneic Haematopoietic Cell Transplantation (HCT)
5. Considered suitable for lymphodepleting chemotherapy
6. The patient's peripheral superficial venous blood flow smoothly, which can meet the needs of intravenous drip.
7. Patient's main organs function well. A. Liver function: ALT/AST \< 3 times the upper limit of normal (ULN); B. total bilirubin≤34.2μmol/L; C. Renal function: Creatinine \< 220μmol/L; D. Pulmonary function: Indoor oxygen saturation≥95%; E. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥40%;
8. Life expectancy of at least 3 months
9. Patient ECOG score≤2, Estimated survival time≥3 months.
10. Ability to be off systemic prednisone and other immunosuppressive drugs for at least 3 days prior to γδ T cells product infusion. Maintenance replacement steroid is allowed.
11. The patients did not receive any anticancer treatments such as chemotherapy, radiotherapy and immunotherapy (such as immunosuppressive drugs) within 4 weeks before admission, and the toxicity related to previous treatments had returned to \< 1 level at admission (except for low toxicity such as alopecia).
12. Patient able to understand and sign written informed consent
13. Age 18 years up to the age of 75 (≤ 75)

Exclusion Criteria:

1. Women who are pregnant (urine/blood pregnancy test positive) or lactating.
2. Male or female with a conception plan in the past 1 years.
3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 years after enrollment.
4. Uncontrolled infectious disease within 4 weeks prior to enrollment.
5. Active hepatitis B/C virus.
6. HIV infected patients.
7. Suffering from a serious autoimmune disease or immunodeficiency disease.
8. The patient is allergic and is allergic to macromolecular biopharmaceuticals such as antibodies or cytokines.
9. The patient participated in other clinical trials within 6 weeks prior to enrollment.
10. Systemic use of hormones within 4 weeks prior to enrollment (except for patients with inhaled corticosteroids).
11. Have a history of epilepsy or other central nervous system diseases.
12. Having drug abuse/addiction.
13. According to the researcher's judgment, the patient has other unsuitable grouping conditions.

Primary outcomes:
measure: Four-months remission rate
timeFrame: 4 months
measure: Number of participants with adverse events (AEs)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years
measure: Event-free survival
timeFrame: 3 years
measure: Relapse-free survival
timeFrame: 3 years
measure: Quantity of gamma-delta T cells in bone marrow cells and peripheral blood cells
timeFrame: 3 years
measure: lymphocyte subsets function assessment of bone marrow cells and peripheral blood cells
timeFrame: 3 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Heng Mei, M.D. Ph.D
role: PRINCIPAL_INVESTIGATOR
References: