ACHIEVE - Efficacy and Effectiveness of Adoptive Cellular tHerapy wIth Ex-Vivo Expanded Allogeneic γδ T-lymphocytes (TCB-008) for Patients With Refractory or Relapsed Acute Myeloid Leukaemia (AML)

• Status: Not yet recruiting
• Trial end date: 2024-05-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an open label, adaptive, efficacy and effectiveness, phase II clinical trial in adult patients with AML with refractory and relapsed disease. An adaptive trial approach with a two-stage Simon design will be utilised for a total of up to 74 adult patients per dose level of TCB008 cells

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: TC Biopharm

Criteria

Inclusion Criteria:

1. Age ≥ 18 to ≤ 75 years

2. Karnofsky performance status ≥ 70% and WHO/ECOG performance status 0 - 1 at enrolment and up to 2 at the time of infusion.

3. Must be able to remain free of systemic corticosteroid (e.g., prednisone) 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.

4. Must be able to understand and sign written informed consent and be willing to participate in a clinical trial for an advanced therapy investigational medicinal product (AT(I)MP) used for adoptive cell therapy (ACT).

5. Women of childbearing potential must receive a pregnancy test within 7 days prior to initiation of treatment with the lymphodepleting regimen and the result must be negative; male and female patients with fertility must use an effective contraceptive for 3 months after the completion or discontinuation of treatment during.

6. Pathologically confirmed diagnosis of AML, or MDS, or CMML or MPN confirmed according to WHO 2016 criteria.

7. For Cohort A1, patients must have AML that is primary refractory defined as not achieving a morphological CR after 1-2 cycles of intensive or non- intensive induction chemotherapy.

8. For Cohort A2, patients with AML must have previously achieved a morphological CR to a maximum of three regimens of previous intensive or non-intensive therapy, then have experienced relapsed AML

9. For Cohort B1, patients with AML who have achieved morphological CR but have persistent MRD.

10. Included patients will not be deprived of standard of care by participating in this trial.

Exclusion Criteria:

1. Suspected or proven active CNS disease.

2. Previous reactions to Fludarabine or Cyclophosphamide, or patients at risk of Fludarabine related neurotoxicity

3. Unable to receive TBI

4. Acute promyelocytic leukaemia

5. Bisphosphonates (≤2 months before study entry)

6. Corticosteroids (cumulative dose of systemic steroids >20mg of prednisolone per day or equivalent) that cannot be discontinued 5 days prior to TCB008 infusion.

7. Antihyperlipidemic medications (e.g., statins) that cannot be discontinued prior to enrolment.

8. Cardiac failure: EF < 40%.

9. Kidney function: creatinine clearance ≤ 60 mL/min

10. Liver function: total bilirubin > 3 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 5 × ULN,

11. Neurological condition(s) which might be exacerbated by therapy or prevent assessments for neurotoxicity/ICANS

12. GVHD of any grade or anti-GVHD treatment.

13. Lung function: symptoms of respiratory failure or < 92% oxygen saturation on air.

14. Active infections that are difficult to control, including positive COVID-19 diagnosis at screening.

15. Received autologous or allogeneic cell therapy within 4 weeks, such as donor lymphocyte infusion.

16. Received autologous or allogeneic gene modified adoptive cell therapy (e.g CAR-T, TCR-T, CAR-NK cell therapy, etc).

17. Subject received anti-tumour treatment (chemotherapy, monoclonal antibody, or hormone) within one week of screening (hydroxycarbamide is permitted until lymphodepletion).

18. Patients who are EBV negative

19. Pregnant or lactating women.

20. Hypersensitivity to iron-dextran or murine antibodies

21. Patients who are active participants in other interventional clinical trials at the same time. Co-enrolment is permitted for non-interventional studies if approved by the CI.

22. The Principal Investigator believes that there are other factors that are not suitable for inclusion or influence the patient's participation or completion of the study.

23. Considered unsuitable for further intensive therapy or expected to survive less than 3 months with conventional available treatments.