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

Phase 1

Completed

• Conditions: Acute Myeloid Leukemia
• Interventions: Biological: OmnImmune®

• Registration Number: NCT03790072
• Lead Sponsor: TC Biopharm

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.

Study Timeline

• Study Start: 2018-11-27
• Study First Submitted: 2018-12-12
• Study First Submitted QC: 2018-12-27
• Study First Posted: 2018-12-31
• Status Verified: 2021-03
• Primary Completion: 2021-03-26
• Study Completion: 2021-03-26
• Last Update Submitted: 2021-03-29
• Last Update Posted: 2021-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment Arm	OmnImmune®	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability]	Day 28 after completion of treatment	Tolerability of OmnImmune® assessed by incidence of dose-limiting toxicities (DLTs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Incidence of Treatment-Emergent Adverse Events (AEs) [Safety]	Day 28 after completion of treatment	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

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) [Efficacy]	24 months post-treatment	Efficacy of OmnImmune® assessed by overall survival (OS) measured in months
Quality of Life (QoL)	24 months post-treatment	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.
Number of patients reaching Complete Remission (CR) [Efficacy]	24 months post-treatment	Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)

Trial Locations

Locations (1)

UHKT (Ustav hematologie a krevni transfuze); 🇨🇿 Praha, Czechia