Ex-vivo Expanded γδ T-lymphocytes (OmnImmune®) in Patients With Acute Myeloid Leukaemia (AML)

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03790072
• Other study ID #: TCB-202-001
• Secondary ID: 2018-000409-22
• Status: Completed
• Phase: Phase 1
• Start date: November 27, 2018
• Est. completion date: March 26, 2021

Study information

• Verified date: March 2021
• Source: TC Biopharm
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 26, 2021
• Est. primary completion date: March 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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 ?d 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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• OmnImmune®
infusion of OmnImmune® (expanded gamma delta T lymphocytes)

Locations

Country	Name	City	State
Czechia	UHKT (Ustav hematologie a krevni transfuze)	Praha

Sponsors (1)

Lead Sponsor	Collaborator
TC Biopharm

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Persistence of ?d T cells	Persistence of ?d T cells assessed by number and phenotype of ?d T cells using flow cytometry assay in peripheral blood and bone marrow from dosed patients	Before treatment and up to 24 months after treatment
Other	Phenotype of ?d T cells	Phenotype of ?d T cells assessed by flow cytometry assay in peripheral blood and bone marrow from dosed patients	Before treatment and up to 24 months after treatment
Primary	Incidence of Treatment-Emergent Adverse Events (AEs) [Safety]	Safety of OmnImmune® assessed by incidence of treatment-emergent adverse events (AEs) per patient graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Day 28 after completion of treatment
Primary	Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability]	Tolerability of OmnImmune® assessed by incidence of dose-limiting toxicities (DLTs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Day 28 after completion of treatment
Secondary	Number of patients reaching Complete Remission (CR) [Efficacy]	Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)	24 months post-treatment
Secondary	Overall Survival (OS) [Efficacy]	Efficacy of OmnImmune® assessed by overall survival (OS) measured in months	24 months post-treatment
Secondary	Quality of Life (QoL)	Quality of life determined by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 'C30' which comprises 30 items (i.e. single questions), 24 of which are aggregated into nine multi-item scales, that is, five functioning scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain and nausea/vomiting) and one global health status scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.	24 months post-treatment