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

University College London (UCL)

Status and phase: Unknown; Phase 1

Conditions: Graft Vs Host Disease; Lymphoma; Myeloma; Primary Immune Deficiency; Leukemia; Myelodysplastic Syndromes; Severe Aplastic Anemia

Treatments: Biological: CD62L- Tem

Study type: Interventional

Funder types: Other

Identifiers

NCT03836690

UCL/13/0372

MR/R025436/1 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full description

Phase I study using a Bayesian Time-to-Event Continual Reassessment Method (CRM) to determine safety and maximum tolerated dose (MTD) of CD62L- Tem.

Eligible patients and HLA-identical sibling donors will be registered prior to stem cell transplant (SCT). Donors will undergo an additional steady state apheresis for the collection of T cells between day -14 and day +24 of the allo-SCT according to logistics. Selection of Tem at the required dose will be performed at UCL Centre for Cell, Gene and Tissue Therapeutics (CCGTT) before distribution of the cryopreserved cells to the trial centre. Doses of Tem selected and infused will be: 1x10^5, 3x10^5, 1x10^6 or 3x10^6.

Donor Tem will be infused on day 24-32 following allo-SCT. Patients will be followed-up for 12 months with specific evaluation points just prior to Tem infusion and at 3, 6, 9 and 12 months following allo-SCT.

Enrollment: 18 estimated patients

Sex: All

Ages: 16 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Donor T cells depleted of CD62L+ cells (CD62L- Tem)

Experimental group

Description:

Donors will undergo a steady state apheresis for the collection of T cells. Selection of CD62L- Tem at the required dose will be performed at UCL Centre for Cell, Gene and Tissue Therapeutics (CCGTT). Donor Tem will be infused into patients on day 24-32 following allo-Stem Cell Transplant.

Treatment:

Biological: CD62L- Tem