ACHIEVE - Efficacy and Effectiveness of Adoptive Cellular tHerapy wIth Ex-Vivo Expanded Allogeneic γδ T-lymphocytes (TCB008) for Patients With Refractory or Relapsed Acute Myeloid Leukaemia (AML)

NCT05358808 | Terminated Phase 2 DMC

• 1 other identifier: TCB008-001
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, phase II study designed to evaluate the efficacy and effectiveness of TCB008 in patients with Acute Myeloid Leukemia (AML), or Myelodysplastic Syndromes (MDS)/AML, with either refractory or relapsed disease. Five patients will be recruited for an initial safety cohort. The safety cohort will be followed by a two-stage Simon's Design, where a further 48 patients will be recruited into one of two cohorts and dosed with TCB008.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Keywords

AML; MDS; MDS/AML; AML/MDS

Outcome Measures

Primary Outcomes (4)

• Reduction in myeloblast levels in response to TCB008 dosing

  Reduction in myeloblast levels compared to baseline, measured according to the ELN AML 2022 Response Criteria.

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Patient relapse and subsequent response to repeat TCB008 dosing

  Measured by the numbers of patients who, after initial response, subsequently relapse and then respond to an additional infusion.

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Overall response rate to TCB008 dosing

  Overall response rate, defined as morphological CR, CRi, Rh, PR, and MLFS at 28-days post-infusion, measured according to the ELN AML 2022 Response Criteria.

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Measurable Residual Disease in response to TCB008 dosing

  MRD-negative remission (CR without MRD or CR MRD-) by multiparameter flow cytometry-based MRD (MFC-MRD) or molecular MRD (Mol-MRD) assessed by qPCR, according to the ELN AML 2022 Response Criteria.

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

Secondary Outcomes (6)

• Severity of adverse events in response to TCB008 dosing

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Incidence and severity of CRS and neurotoxicity in response to TCB008 dosing

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Overall survival rates following TCB008 dosing

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Relapse-free survival following TCB008 dosing

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

• Event-free survival following TCB008 dosing

  The total duration of study participation for each patient (from screening through end of study visit) is anticipated to be approximately 15 months).

Study Arms (1)

γδ T cells (IMP, TCB008)

EXPERIMENTAL

After inclusion, all patients will receive lymphodepleting chemotherapy with fludarabine 30mg/m2 Day -6 to Day -3 \[total 120 mg/m2\] and cyclophosphamide 0.5g/m2 \[total 1.5 g/m2) Day -5 to Day -3,\]. This will be followed by a rest day (Day -2). The first five patients (safety cohort) will receive 1.8mL of TCB008 (containing 3.5x10\^7 to 11.0x10\^7 cells) on Day 0. After treatment of the first five safety patients, the remaining 48 patients will receive 5mL of TCB008 (containing 12.0x10\^7 to 23.0x10\^7 cells) on Day 0.

Drug: TCB008

Interventions

TCB008 DRUG

TCB008 is derived from the peripheral blood mononuclear cells (PBMCs) of unrelated, healthy donors and consists of expanded cluster designation (CD)3+ T cells expressing the γ chain variable region 9 δ-chain variable region 2 (Vγ9Vδ2) T cell receptor (TCR); it is infused into patients to boost their immune system. It is currently developed for treatment of cancers and infectious diseases.

Also known as: CD3+ T cells expressing the γ-chain variable region 9 δ-chain variable region 2 (Vγ9Vδ2) T cell receptor (TCR)

γδ T cells (IMP, TCB008)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 at the time of consent
• Karnofsky performance status ≥ 70% and WHO/ECOG performance status 0 -1 at enrolment and up to 2 at the time of infusion.
• Must be able to remain free of systemic corticosteroid (e.g., prednisolone) and other immunosuppressive therapy at screening and for at least 5 days prior to the infusion of γδ T cells. Maintenance replacement steroid after assessment of the primary endpoint is permitted.
• Must be able to understand and sign written informed consent and willing to participate in a clinical trial for an advanced therapy investigational medicinal product (AT(I)MP).
• For women of childbearing potential, a urine or serum pregnancy test will be performed within 7 days prior to initiating lymphodepletion. A serum pregnancy test will be performed on the day prior to the first infusion of TCB008 (i.e. day -1) and urine or serum pregnancy tests will be performed on the day of subsequent infusions with TCB008 and the results must be negative at all times that these pregnancy tests are performed. For women of childbearing potential, a serum pregnancy test will be performed at visit 17 or early termination. Patient and his/her partner must agree to use adequate contraception from the time of providing written consent through 3 months after the last study drug dose
• Pathologically confirmed diagnosis of AML or MDS/AML confirmed according to ELN 2022 Criteria (as per International Consensus Classification of AML).
• For Cohort A1, patients must have AML or MDS/AML that is primary refractory defined as not achieving a CR, CRi or CRh after 2 cycles of intensive or non-intensive induction chemotherapy.
• For Cohort A2, patients with AML or MDS/AML must have previously achieved a CR, CRi or CRh (including MRD negative CR) to previous intensive or non-intensive therapy, then have experienced relapsed AML.
• For Cohort B, patients with AML who have achieved CR, CRi or CRh but have persistent MRD by multiparameter flow cytometry-based MRD (MFC-MRD) or molecular MRD (Mol-MRD) assessed by qPCR.
• Included patients will not be deprived of standard of care by participating in this trial.

You may not qualify if:

• Suspected or proven active CNS disease.
• Previous reactions to Fludarabine or Cyclophosphamide or patients at risk of Fludarabine related neurotoxicity
• Acute promyelocytic leukaemia
• Bisphosphonates (≤8 weeks before study entry), unless continued as a standard of care medication
• Corticosteroids (cumulative dose of systemic steroids \>20mg of prednisolone per day or equivalent) that cannot be discontinued 5 days prior to TCB008 infusion.
• Antihyperlipidemic medications (e.g., statins) that cannot be discontinued prior to enrolment.
• Cardiac failure: EF \< 40%.
• Kidney function: creatinine clearance ≤ 60 mL/min.
• Liver function: total bilirubin \> 3 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 5 × ULN.
• Neurological condition(s) which might be exacerbated by therapy or prevent assessments for neurotoxicity/ICANS.
• GVHD of any grade or anti-GVHD treatment.
• Lung function: symptoms of respiratory failure or \< 92% oxygen saturation on air.
• Active infections that are difficult to control, including positive COVID-19 diagnosis at screening. NOTE: Active infections following lymphodepletion may exclude a patient from being able to be dosed with IMP.
• Received autologous or allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion.
• Received autologous or allogeneic gene modified adoptive cell therapy (e.g. CAR-T, TCR-T, CAR-NK cell therapy, etc).

Sponsors & Collaborators

• TC Biopharm: lead

Study Sites (6)

Bristol and Weston NHS foundation trust

Bristol, BS2 8ED, United Kingdom

Location

Cardiff and Vale University LHB

Cardiff, CF14 4HH, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, G51 4TF, United Kingdom

Location

Guys&St Thomas NHS foundation Trust

London, SE1 7EH, United Kingdom

Location

Kings College Hospital

London, SE5 9RS, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Receptors, Antigen, T-Cell

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Receptors, Antigen; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Emma Nicholson, MD

  Royal Marsden Hospital London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 3, 2022
• Study Start: August 15, 2022
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

GB (6)