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) — ACHIEVE  

Acute Myeloid Leukemia Clinical Trial

Official title: ACHIEVE - An Adaptive Trial of the 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)

Status Recruiting

Clinical Trial 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.

Clinical Trial Description

TCB008-001 (ACHIEVE) 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.

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.

53 patients will take part in this study; five patients in an initial safety cohort followed by a two-stage Simon's Design that will recruit a further 48 patients into one of two patient cohorts.

Patients will be screened to assess their eligibility to enter the study 35 days prior to the first dose of the investigational medicinal product (IMP). Once enrolled in the study, patients will undergo lymphodepletion chemotherapy prior to administration of the IMP using the following regimen: fludarabine (30mg/m2/day) will be administered from days -6 to -3 (total 120mg/m2), and cyclophosphamide (0.5g/m2/day) from days -5 to -3 (total 1.5g/m2). No chemotherapy will be administered on days -2 and -1.

Cohort A will recruit patients with relapsed or refractory AML or MDS/AML. These patients will be split between one of two sub-cohorts;

• Cohort A1 will include patients with primary refractory AML or MDS/AML who have not achieved a CR, CRi, or CRh after two cycles of induction chemotherapy.

• Cohort A2 will include patients with AML or MDS/AML who have relapsed after initially achieving a CR, CRi, or CRh to previous chemotherapy.

This cohort would include MDS/AML patients with 10 to 19% blast levels in the bone marrow or peripheral blood as defined in the European Leukemia Net 2022 Criteria (as per international consensus classification of AML).

Cohort B will recruit patients with AML or MDS/AML who have achieved CR, CRi, or CRh but have a detectable measurable residual disease by MFC-MFD or Mol-RD by qPCR.

Patients may receive repeat infusions of TCB008, on up to three occasions, 14 days after the previous infusion. Re-infusions will not be preceded by lymphodepleting chemotherapy.

Patients will be followed for up to 52 weeks following the first infusion of TCB008, or until either; they are lost to follow-up, or early termination. Blood and bone marrow samples will be taken pre- and post-infusion to evaluate the study objectives and endpoints.

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes

• NCT number: NCT05358808
• Study type: Interventional
• Source: TC Biopharm
• Contact: Emma Nicholson, MD
• Phone: +44 02086613018
• Email: emma.nicholson@rmh.nhs.uk
• Status: Recruiting
• Phase: Phase 2
• Start date: August 15, 2022
• Completion date: December 2025