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

Primary Purpose

Lymphoma, Leukemia, Myeloma

Status
Unknown status
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
CD62L- Tem
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma

Eligibility Criteria

16 Years - 70 Years (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • UCLHRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

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

Arm 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.

Outcomes

Primary Outcome Measures

Occurrence of dose limiting toxicity (DLT)
Occurrence of dose limiting toxicity (DLT) (defined as acute-pattern GvHD grade II-IV)

Secondary Outcome Measures

Incidence and severity of acute GvHD
Incidence and severity of acute GvHD (whether dose limiting or not)
Incidence and severity of chronic GvHD
Incidence and severity of chronic GvHD
Non-relapse mortality
Death without reoccurrence of cancer
Overall survival
Death
Progression-free survival
Disease progression or death
Incidence/type of infection requiring inpatient admission
Any infection that has required an inpatient admission, incidence and type of infection
Total Number of inpatient days
Total Number of inpatient days for any reason

Full Information

First Posted
January 10, 2019
Last Updated
October 22, 2019
Sponsor
University College, London
Collaborators
Medical Research Council
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1. Study Identification

Unique Protocol Identification Number
NCT03836690
Brief Title
Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
Acronym
ToTem
Official Title
Phase I Study of Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 21, 2019 (Actual)
Primary Completion Date
July 1, 2022 (Anticipated)
Study Completion Date
April 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Medical Research Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Leukemia, Myeloma, Myelodysplastic Syndromes, Severe Aplastic Anemia, Primary Immune Deficiency, Graft Vs Host Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Donor T cells depleted of CD62L+ cells (CD62L- Tem)
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
CD62L- Tem
Intervention Description
Donor memory T cells that have been depleted of CD62L+
Primary Outcome Measure Information:
Title
Occurrence of dose limiting toxicity (DLT)
Description
Occurrence of dose limiting toxicity (DLT) (defined as acute-pattern GvHD grade II-IV)
Time Frame
up to 72 days after Tem infusion
Secondary Outcome Measure Information:
Title
Incidence and severity of acute GvHD
Description
Incidence and severity of acute GvHD (whether dose limiting or not)
Time Frame
From date of infusion of Tem until 100 days post stem cell transplant
Title
Incidence and severity of chronic GvHD
Description
Incidence and severity of chronic GvHD
Time Frame
From date of infusion of Tem up to 1 year post stem cell transplant
Title
Non-relapse mortality
Description
Death without reoccurrence of cancer
Time Frame
From date of patient registration up to 1 year post stem cell transplant
Title
Overall survival
Description
Death
Time Frame
From date of patient registration up to 1 year post stem cell transplant
Title
Progression-free survival
Description
Disease progression or death
Time Frame
From date of patient registration up to 1 year post stem cell transplant
Title
Incidence/type of infection requiring inpatient admission
Description
Any infection that has required an inpatient admission, incidence and type of infection
Time Frame
From date of infusion of Tem up to 1 year post stem cell transplant
Title
Total Number of inpatient days
Description
Total Number of inpatient days for any reason
Time Frame
From date of infusion of Tem up to 1 year post stem cell transplant
Other Pre-specified Outcome Measures:
Title
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
Title
Chimerism of immune subsets (analysing the genetic profiles of recipient and donor at baseline and following stem cell transplant)
Description
Identifying the genetic profiles of the recipient and of the donor at baseline, evaluating changes in this following stem cell transplant
Time Frame
Pre-Registration and Day 100, 180, 270, 360 post stem cell transplant
Title
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)
Description
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
Time Frame
Day 100, 180, 270, 360 post stem cell transplant
Title
Difference between donor immune profile with number of CD62L- Tem selected
Description
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).
Time Frame
Day -14 to -7 (day of cell processing)
Title
Alemtuzumab levels on the day of CD62L- Tem infusion
Time Frame
Day 28 post stem cell transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toyin Adedayo
Phone
0207 679 9867
Email
ctc.totem@ucl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Nadjet El-Mehidi
Phone
0207 679 9283
Email
ctc.totem@ucl.ac.uk
Facility Information:
Facility Name
UCLH
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ron Chakraverty, Prof

12. IPD Sharing Statement

Plan to Share IPD
No

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

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