LymphomaPhase 1ToTemNCT03836690
Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
A Phase 1 study testing CD62L- Tem in people with Lymphoma and Leukemia, run by University College, London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 70 yearsHealthy volunteers can take part
- What is being tested?
- CD62L- Tem
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 21 Oct 2019to 1 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 70 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
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 locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
UCLH
London
Ron Chakraverty, Prof
About this study
Official title: Phase I Study of Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
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.
Read the 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.
- Conditions
- Lymphoma, Leukemia, Myeloma, Myelodysplastic Syndromes, Severe Aplastic Anemia, Primary Immune Deficiency
- Being tested
- CD62L- Tem
- Medical subject headings
- Lymphoma, Leukemia, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Anemia, Aplastic, Primary Immunodeficiency Diseases, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD62L- TemBiological
Donor memory T cells that have been depleted of CD62L+
| Study group | Role | What they receive |
|---|---|---|
| Donor T cells depleted of CD62L+ cells (CD62L- Tem) | Experimental | 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. Receives: Biological: CD62L- Tem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of dose limiting toxicity (DLT)
Occurrence of dose limiting toxicity (DLT) (defined as acute-pattern GvHD grade II-IV)
Measured: up to 72 days after Tem infusion
Secondary outcomes (7)
Incidence and severity of acute GvHD
Incidence and severity of acute GvHD (whether dose limiting or not)
Measured: From date of infusion of Tem until 100 days post stem cell transplant
Incidence and severity of chronic GvHD
Incidence and severity of chronic GvHD
Measured: From date of infusion of Tem up to 1 year post stem cell transplant
Non-relapse mortality
Death without reoccurrence of cancer
Measured: From date of patient registration up to 1 year post stem cell transplant
Overall survival
Death
Measured: From date of patient registration up to 1 year post stem cell transplant
Progression-free survival
Disease progression or death
Measured: From date of patient registration up to 1 year post stem cell transplant
Incidence/type of infection requiring inpatient admission
Any infection that has required an inpatient admission, incidence and type of infection
Measured: From date of infusion of Tem up to 1 year post stem cell transplant
Total Number of inpatient days
Total Number of inpatient days for any reason
Measured: From date of infusion of Tem up to 1 year post stem cell transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2019
- Study start21 Oct 2019
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Apr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03836690
- Sponsor's protocol ID
- UCL/13/0372
- Other IDs
- MR/R025436/1
- Acronym
- ToTem
- Status last verified
- Oct 2019
- First submitted
- 10 Jan 2019
- Last updated
- 25 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03836690
- Acronym / sponsor ID
- ToTem / UCL/13/0372
- Conditions
- Lymphoma, Leukemia, Myeloma, Myelodysplastic Syndromes, Severe Aplastic Anemia, Primary Immune Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- 21 Oct 2019 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Apr 2023 (estimated)
- First posted
- 11 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Donor T cells depleted of CD62L+ cells (CD62L- Tem) | Experimental | Biological: CD62L- TemDonors 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. |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD62L- TemDonor memory T cells that have been depleted of CD62L+ | Biological | Donor T cells depleted of CD62L+ cells (CD62L- Tem) |
Primary outcome
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)
7 secondary outcomes
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 chronic GvHD
Time frame: From date of infusion of Tem up to 1 year post stem cell transplant
Non-relapse mortality
Time frame: From date of patient registration up to 1 year post stem cell transplant
Overall survival
Time frame: From date of patient registration up to 1 year post stem cell transplant
Progression-free survival
Time frame: From date of patient registration up to 1 year post stem cell transplant
Incidence/type of infection requiring inpatient admission
Time frame: From date of infusion of Tem up to 1 year post stem cell transplant
Total Number of inpatient days
Time frame: From date of infusion of Tem up to 1 year post stem cell transplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD62L- Tem in people with Lymphoma and Leukemia, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Toyin Adedayo (0207 679 9867, ctc.totem@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of dose limiting toxicity (DLT) (time frame: up to 72 days after Tem infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2019.