Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation (ToTem)

 Aplastic Anemia / Posted 1 year ago

RATIONALE: Following stem cell transplantation, a major risk is graft-versus-host disease (GVHD). This occurs when donor immune cells that have been infused recognise the host’s cells as ‘foreign’ and attack these cells. Prevention of GVHD relies upon depletion of donor immune T cells or drugs that block T cell function. However, these methods also increase the risk of life threatening infection. There is an important unmet need for better means of accelerating immune recovery following stem cell transplantation while avoiding GVHD.

Pre-clinical studies have shown that infusion of donor CD62L- effector memory T cells (Tem) into the host improve immune recovery after allo-Stem Cell Transplant but do not cause GVHD.

PURPOSE: This phase I dose escalation trial aims to determine the feasibility and safety of transfer of donor Tem following allogeneic stem cell transplantation.

  • Inclusion Criteria : Ages Eligible for Study: 16 Years to 70 Years (Child, Adult, Older Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: Yes Patient Registration Inclusion Criteria:
    • Severe aplastic anaemia or
    • Primary immune deficiency or
    • Haematological cancer which can be ONE OF the following: - Non-Hodgkin's lymphoma (NHL) in CR or PR; - Hodgkin's lymphoma (HL) in CR or PR; - Chronic (Pro-)lymphocytic leukaemia (CLL or PLL) in CR or PR - Plasma cell myeloma (PCM) in CR, VGPR or PR; - Acute myeloid leukaemia (AML) in CR; - Acute lymphoblastic leukaemia (ALL) in CR; - Myelodysplastic syndrome (MDS) < 10 % blasts in bone marrow; - Chronic myelomonocytic leukaemia (CMML) < 10% blasts in bone marrow
    • Suitable for HLA-identical sibling transplant using a standard alemtuzumab-based conditioning regimen with calcineurin-inhibitor based immunoprophylaxis
    • Aged ≥ 16 years, <70 years
    • Written informed consent
  • Exclusion Criteria : Patient Registration Exclusion Criteria:
    • Women who are pregnant or breast-feeding
    • Life expectancy of < 8 weeks
    • Currently taking part in any other interventional clinical research study (involving any IMP, ATMP or cellular therapy)
    • Proposed use of any other method of GVHD prophylaxis other than alemtuzumab and calcineurin inhibitor
    • Organ dysfunction: - LVEF<45% - Creatinine >200 µmol/lglomerular filtration rate (corrected) <50ml/min - Bilirubin > 50 µmol/l - AST or ALT >3x 2.5 x ULN (NB: If both are performed then both must be ≤3 2.5 x ULN) Patient Trial Treatment Exclusion criteria:
    • Prior or active acute pattern GvHD of any grade
    • Relapse or progression
    • Primary or secondary graft failure
    • Has received other cellular therapies Donor inclusion criteria:
    • Aged ≥ 16 years
    • HLA-identical sibling
    • Have met transplant centre criteria regarding suitability for cell therapy donation
    • Negative for HIV 1 and 2, hepatitis B, hepatitis C, HTLV-1 and 2, syphilis serology (to be confirmed before both registration and before trial treatmentat time of or up to 7 days following donation)
    • Written informed consent Donor exclusion criteria: - Pregnant/lactating women
  • Study end date : 01/04/2023
  • Wales-Based Study Contact : Please speak to your clinician
  • Principal Investigator : Ron Chakraverty, Prof
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