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

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

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

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: OmnImmune®

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Praha, Czechia, 128 20
    • UHKT (Ustav hematologie a krevni transfuze)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; After inclusion, patients will receive conditioning chemotherapy consisting of non-investigational medicinal products (non-IMPs): fludarabine 25 mg/m2 from day -6 until day -2 (inclusive) and cyclophosphamide 500 mg/m2 on days -6 and -5. Subsequently, patients in will be dosed with investigational medicinal product (IMP) OmnImmune® on day 0.	Biological: OmnImmune®; infusion of OmnImmune® (expanded gamma delta T lymphocytes); Other Names: cyclophosphamide; fludarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients reaching Complete Remission (CR) [Efficacy]	Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)	24 months post-treatment
Overall Survival (OS) [Efficacy]	Efficacy of OmnImmune® assessed by overall survival (OS) measured in months	24 months post-treatment
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistence of γδ T cells	Persistence of γδ T cells assessed by number and phenotype of γδ T cells using flow cytometry assay in peripheral blood and bone marrow from dosed patients	Before treatment and up to 24 months after treatment
Phenotype of γδ T cells	Phenotype of γδ 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

Collaborators and Investigators

• Sponsor: TC Biopharm

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2018
• Primary Completion (Actual): March 26, 2021
• Study Completion (Actual): March 26, 2021

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (Actual): December 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 29, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Gamma Delta T Lymphocytes
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: TCB-202-001; 2018-000409-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No