Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
ToTem
Phase I Study of Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
2 other identifiers
interventional
18
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 lymphoma
Started Oct 2019
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 10, 2019
CompletedFirst Posted
Study publicly available on registry
February 11, 2019
CompletedStudy Start
First participant enrolled
October 21, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2023
CompletedOctober 25, 2019
October 1, 2019
2.7 years
January 10, 2019
October 22, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Occurrence of dose limiting toxicity (DLT)
Occurrence of dose limiting toxicity (DLT) (defined as acute-pattern GvHD grade II-IV)
up to 72 days after Tem infusion
Secondary Outcomes (7)
Incidence and severity of acute GvHD
From date of infusion of Tem until 100 days post stem cell transplant
Incidence and severity of chronic GvHD
From date of infusion of Tem up to 1 year post stem cell transplant
Non-relapse mortality
From date of patient registration up to 1 year post stem cell transplant
Overall survival
From date of patient registration up to 1 year post stem cell transplant
Progression-free survival
From date of patient registration up to 1 year post stem cell transplant
- +2 more secondary outcomes
Other Outcomes (5)
TCR repertoire analysis by deep CDR3 sequencing
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)
Pre-Registration and Day 100, 180, 270, 360 post 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)
Day 100, 180, 270, 360 post stem cell transplant
- +2 more other outcomes
Study Arms (1)
Donor T cells depleted of CD62L+ cells (CD62L- Tem)
EXPERIMENTALDonors 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.
Interventions
Donor memory T cells that have been depleted of CD62L+
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
- Prior or active acute pattern GvHD of any grade
- Relapse or progression
- Primary or secondary graft failure
- Has received other cellular therapies
- Aged ≥ 16 years
- HLA-identical sibling
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Medical Research Councilcollaborator
Study Sites (1)
UCLH
London, United Kingdom
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 10, 2019
First Posted
February 11, 2019
Study Start
October 21, 2019
Primary Completion
July 1, 2022
Study Completion
April 1, 2023
Last Updated
October 25, 2019
Record last verified: 2019-10
Data Sharing
- IPD Sharing
- Will not share