Clinical trial NCT03790072: Ex-vivo Expanded γδ T-lymphocytes (OmnImmune®) in Patients With Acute Myeloid Leukaemia (AML)
Official title: Safety and Efficacy of Ex-vivo Expanded Allogeneic γδ T-lymphocytes (OmnImmune®) in Patients With Active Relapsed or Refractory Acute Myeloid Leukaemia (AML) Who Are Not Eligible for or do Not Consent to High Dose Salvage Chemotherapy and/or Allogeneic Haematopoietic Cell Transplantation (HCT). A Dose Escalation, Open-label, Phase I Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Gamma Delta T Lymphocytes
Lead sponsor: TC Biopharm
Sponsor class: INDUSTRY
First posted: 2018-12-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation, 3 cohorts, x10 dose increments between cohorts (10\^6, 10\^7, 10\^8 of cells per kg of body weight).
Primary purpose: TREATMENT

Brief summary: This study investigates the potential curative properties of gamma delta T-cells obtained from a blood-related donor of an AML patient.

Detailed description: This is an open-label, safety and efficacy, escalating dose, single arm study on 9 adult subjects (3 cohorts) and 3+3 design will be used. HLA typed patients and potential blood-related donors will be screened for comorbidities. Suitably matched or haploidentical family donors will be selected according to protocol specified criteria and institutional guidelines of participating site.

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

   1. AML relapse after intensive chemotherapy OR
   2. AML relapse after allogeneic HCT OR
   3. AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or decitabine) OR
   4. No response to at least 4 cycles of low intensity therapy
   5. 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. Age 18 years up to the age of 70 (≤ 70)
7. Life expectancy of at least 3 months
8. Karnofsky performance status ≥ 50%
9. Available related HLA-haploidentical or HLA-matched donor
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. Patient able to understand and sign written informed consent

Exclusion Criteria:

1. Uncontrolled infections
2. Renal insufficiency: creatinine \> 180 μmol/L or on dialysis
3. Heart failure: EF \< 40%
4. Respiratory insufficiency: oxygen therapy required at inclusion in the study
5. Significant liver impairment: bilirubin \> 50 μmol/L, AST or ALT \> 4 times normal upper limit
6. Treatment with bisphosphonates (2 months before start)
7. Active autoimmune disease or GvHD
8. Pregnant or breastfeeding
9. Patient of fertile age not using two-barrier method of birth control.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (AEs) [Safety]
timeFrame: Day 28 after completion of treatment
measure: Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability]
timeFrame: Day 28 after completion of treatment
Secondary outcomes:
measure: Number of patients reaching Complete Remission (CR) [Efficacy]
timeFrame: 24 months post-treatment
measure: Overall Survival (OS) [Efficacy]
timeFrame: 24 months post-treatment
measure: Quality of Life (QoL)
timeFrame: 24 months post-treatment
Other outcomes:
measure: Persistence of γδ T cells
timeFrame: Before treatment and up to 24 months after treatment
measure: Phenotype of γδ T cells
timeFrame: Before treatment and up to 24 months after treatment
Locations:
city: Praha
country: Czechia
facility: UHKT (Ustav hematologie a krevni transfuze)
Study officials:
References: