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

Primary Purpose

Acute Myeloid Leukemia

Status

Completed

Phase

Phase 1

Locations

Czechia

Study Type

Interventional

Intervention

OmnImmune®

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Gamma Delta T Lymphocytes

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)
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
Presence of > 5% of blasts in bone marrow or peripheral blood smear
Patient not eligible for or does not consent to high dose salvage chemotherapy and/or allogeneic Haematopoietic Cell Transplantation (HCT)
Considered suitable for lymphodepleting chemotherapy
Age 18 years up to the age of 70 (≤ 70)
Life expectancy of at least 3 months
Karnofsky performance status ≥ 50%
Available related HLA-haploidentical or HLA-matched donor
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.
Patient able to understand and sign written informed consent

Exclusion Criteria:

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

Sites / Locations

UHKT (Ustav hematologie a krevni transfuze)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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

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

Secondary Outcome Measures

Number of patients reaching Complete Remission (CR) [Efficacy]

Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)

Overall Survival (OS) [Efficacy]

Efficacy of OmnImmune® assessed by overall survival (OS) measured in months

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.

Full Information

NCT ID

NCT03790072

First Posted

December 12, 2018

Last Updated

March 29, 2021

Sponsor

TC Biopharm

1. Study Identification

Unique Protocol Identification Number

NCT03790072

Brief Title

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

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

November 27, 2018 (Actual)

Primary Completion Date

March 26, 2021 (Actual)

Study Completion Date

March 26, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

TC Biopharm

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Gamma Delta T Lymphocytes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Dose escalation, 3 cohorts, x10 dose increments between cohorts (10^6, 10^7, 10^8 of cells per kg of body weight).

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment Arm

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

OmnImmune®

Other Intervention Name(s)

fludarabine, cyclophosphamide

Intervention Description

infusion of OmnImmune® (expanded gamma delta T lymphocytes)

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events (AEs) [Safety]

Description

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

Time Frame

Day 28 after completion of treatment

Title

Incidence of Dose-Limiting Toxicities (DLTs) [Tolerability]

Description

Tolerability of OmnImmune® assessed by incidence of dose-limiting toxicities (DLTs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Time Frame

Day 28 after completion of treatment

Secondary Outcome Measure Information:

Title

Number of patients reaching Complete Remission (CR) [Efficacy]

Description

Efficacy of OmnImmune® assessed by number of patients reaching Complete Remission (CR)

Time Frame

24 months post-treatment

Title

Overall Survival (OS) [Efficacy]

Description

Efficacy of OmnImmune® assessed by overall survival (OS) measured in months

Time Frame

24 months post-treatment

Title

Quality of Life (QoL)

Description

Time Frame

24 months post-treatment

Other Pre-specified Outcome Measures:

Title

Persistence of γδ T cells

Description

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

Time Frame

Before treatment and up to 24 months after treatment

Title

Phenotype of γδ T cells

Description

Phenotype of γδ T cells assessed by flow cytometry assay in peripheral blood and bone marrow from dosed patients

Time Frame

Before treatment and up to 24 months after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Relapsed or refractory AML AML relapse after intensive chemotherapy OR AML relapse after allogeneic HCT OR AML progression on low intensity therapy (low dose cytarabine, 5-azacytidine or decitabine) OR No response to at least 4 cycles of low intensity therapy AML refractory to 2 cycles of induction chemotherapy Presence of > 5% of blasts in bone marrow or peripheral blood smear Patient not eligible for or does not consent to high dose salvage chemotherapy and/or allogeneic Haematopoietic Cell Transplantation (HCT) Considered suitable for lymphodepleting chemotherapy Age 18 years up to the age of 70 (≤ 70) Life expectancy of at least 3 months Karnofsky performance status ≥ 50% Available related HLA-haploidentical or HLA-matched donor 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. Patient able to understand and sign written informed consent Exclusion Criteria: Uncontrolled infections Renal insufficiency: creatinine > 180 μmol/L or on dialysis Heart failure: EF < 40% Respiratory insufficiency: oxygen therapy required at inclusion in the study Significant liver impairment: bilirubin > 50 μmol/L, AST or ALT > 4 times normal upper limit Treatment with bisphosphonates (2 months before start) Active autoimmune disease or GvHD Pregnant or breastfeeding Patient of fertile age not using two-barrier method of birth control.

Facility Information:

Facility Name

UHKT (Ustav hematologie a krevni transfuze)

City

Praha

ZIP/Postal Code

128 20

Country

Czechia

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

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

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