Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation (ToTem)
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|ClinicalTrials.gov Identifier: NCT03836690|
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : February 11, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma Leukemia Myeloma Myelodysplastic Syndromes Severe Aplastic Anemia Primary Immune Deficiency Graft Vs Host Disease||Biological: CD62L- Tem||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Study of Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation|
|Estimated Study Start Date :||June 1, 2019|
|Estimated Primary Completion Date :||March 1, 2022|
|Estimated Study Completion Date :||December 1, 2022|
Experimental: Donor T cells depleted of CD62L+ cells (CD62L- Tem)
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.
Biological: CD62L- Tem
Donor memory T cells that have been depleted of CD62L+
- Occurrence of dose limiting toxicity (DLT) [ Time Frame: up to 72 days after Tem infusion ]Occurrence of dose limiting toxicity (DLT) (defined as acute-pattern GvHD grade II-IV)
- Incidence and severity of acute GvHD [ Time Frame: From date of infusion of Tem until 100 days post stem cell transplant ]Incidence and severity of acute GvHD (whether dose limiting or not)
- Incidence and severity of chronic GvHD [ Time Frame: From date of infusion of Tem up to 1 year post stem cell transplant ]Incidence and severity of chronic GvHD
- Non-relapse mortality [ Time Frame: From date of patient registration up to 1 year post stem cell transplant ]Death without reoccurrence of cancer
- Overall survival [ Time Frame: From date of patient registration up to 1 year post stem cell transplant ]Death
- Progression-free survival [ Time Frame: From date of patient registration up to 1 year post stem cell transplant ]Disease progression or death
- Incidence/type of infection requiring inpatient admission [ Time Frame: From date of infusion of Tem up to 1 year post stem cell transplant ]Any infection that has required an inpatient admission, incidence and type of infection
- Total Number of inpatient days [ Time Frame: From date of infusion of Tem up to 1 year post stem cell transplant ]Total Number of inpatient days for any reason
- TCR repertoire analysis by deep CDR3 sequencing [ Time Frame: Day -14 to -7 (day of cell processing) and day 100 and 360 post stem cell transplant ]
- Chimerism of immune subsets (analysing the genetic profiles of recipient and donor at baseline and following stem cell transplant) [ Time Frame: Pre-Registration and Day 100, 180, 270, 360 post stem cell transplant ]Identifying the genetic profiles of the recipient and of the donor at baseline, evaluating changes in this following stem cell transplant
- Assessing the reconstitution level of virus- and bacterial-specific immunity (by measuring the levels of immune cells involved in virus- and bacterial immunity post Tem Infusion) [ Time Frame: Day 100, 180, 270, 360 post stem cell transplant ]Measuring the levels of immune cells at specific points in follow up to determine how virus- and bacterial-specific immunity recovers in patients following a stem cell transplant and Tem infusion
- Difference between donor immune profile with number of CD62L- Tem selected [ Time Frame: Day -14 to -7 (day of cell processing) ]Analysing the donors immune profile pre and post CD62L- Tem selection (cell processing), against the cohort the patient is in (which dose of CD62L- Tem they will receive).
- Alemtuzumab levels on the day of CD62L- Tem infusion [ Time Frame: Day 28 post stem cell transplant ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03836690
|Contact: Toyin Adedayo||0207 679 firstname.lastname@example.org|
|Contact: Nadjet El-Mehidi||0207 679 email@example.com|