Myelodysplastic Syndromes (MDS)Phase 1/2NCT02550535
A Phase I/II Study of Gene-modified WT1 TCR Therapy in MDS & AML Patients
A Phase 1/2 study testing Autologous WT1 TCR transduced T cells in people with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukaemia (AML), run by Cell Medica Ltd at 6 sites in 3 countries.
Trial summary
This is a Phase I/II trial to determine safety, clinical efficacy and feasibility of a gene-modified WT1 TCR therapy in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes (MDS), Acute Myeloid Leukaemia (AML)
- What is being tested?
- Autologous WT1 TCR transduced T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 6 sitesin 3 countries
- Study dates
- Sep 2015to May 2018
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The trial will recruit subjects with MDS or AML who have received hypomethylating agent therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine), and are EITHER:
- Relapsed, defined as failing to maintain an initial IWG response
- OR
- Stable, defined as failing to achieve an IWG response
- Subjects who have received hypomethylating agent therapy as part of a combination regimen may be eligible after discussion with the Sponsor.
- Subjects aged 18 years or older who have a diagnosis of, EITHER:
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- MDS with an IPSS of intermediate -2, or high and one of the following FAB types:
- Refractory anaemia with excess blasts (RAEB)
- Chronic myelomonocytic leukaemia (CMML) with at least 10% bone marrow blasts (WHO CMML II) OR
- AML (diagnosed according to WHO classification 2008 revision)
- Subjects with documented HLA-A*0201 positive serotype
- Subjects with less than 30 per cent bone marrow blasts
- Subjects with relapsed disease must have less than 5 per cent peripheral blasts
- Subjects with stable disease must have less than 10 per cent peripheral blasts
- Subjects with less than a doubling of bone marrow blast count between the start of hypomethylating agent therapy and the date of screening
- Subjects to complete screen 1 visit within a minimum of 28 days and maximum of 90 days since completion of azacitidine or decitabine therapy. Subjects who have exceeded the 90 day window may be eligible after discussion with the Sponsor.
- Subjects with ECOG status 0, 1 or 2
- Subjects who have at least one cytopenia (ANC <1000/μL, platelet count <75,000/μL, Hgb <11g/dL or RBC transfusion dependence)
Who cannot join
- improvement or molecular response following azacitidine treatment
- CMML patients who have a white blood cell count > 13 x 109/L
- Acute promyelocytic leukaemia (FAB M3 Classification)
- Uncontrolled intercurrent illness
- Active malignancy, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
- Known history of Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) or Hepatitis B virus (HBV) or positive for Human T-Lymphocyte Virus (HTLV) or Syphilis. • Active auto-immune disease
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- Clinically significant non-hematologic toxicity after prior therapy chemotherapy higher than grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0)
- Subjects who require haemodialysis or peritoneal dialysis
- Pregnant and lactating women
- Subjects unwilling or unable to use adequate contraceptive precautions at screening and throughout the trial
- Subjects who have undergone major surgery without full recovery within last 28 days prior to screening
- Subjects with known hypersensitivity to cyclophosphamide, fludarabine, methylprednisolone or IL-2 (Interleukin-2)
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United Kingdom3 sites
University Hospitals Bristol NHS Foundation Trust
Bristol, BS2 8ED
The Leeds Teaching Hospitals NHS Trust
Leeds, LS2 9LN
University College London Hospitals NHS Trust
London, NW1 2PG
Belgium2 sites
AZ St Jan Brugge-Oostende AV
Bruges, B-8000
UZ Leuven
Leuven, B - 3000
About this study
Official title: Single Arm Phase I/II Study of the Safety and Efficacy of Gene-modified WT1 TCR Therapy in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukaemia (AML) Who Have Failed to Achieve or Maintain an IWG Response Following Hypomethylating Agent Therapy
This is a Phase I/II trial to determine safety, clinical efficacy and feasibility of a gene-modified WT1 TCR therapy in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
Patient's white blood cells (T cells) will be modified by transferring a gene which enables them to make a new T cell receptor (TCR) that can recognize fragments of a protein called WT1 (Wilms' tumour 1) which is present at abnormally high levels on the surface of myelodysplastic and leukaemic cells.
In this trial, approximately 25 participants with an Human Leukocyte Antigen A2 (HLA-A*0201) tissue type who have failed to achieve or maintain an IWG defined response following hypomethylating agent therapy will be recruited.
Read the detailed description
This is a Phase I/II trial to determine safety, clinical efficacy and feasibility of a gene-modified WT1 TCR therapy. Following provision of informed consent, each subject will undergo screening assessments, including HLA-A*0201 screening (if not already documented) and a bone marrow aspirate/biopsy (BMA) to determine subject eligibility for the trial.
Subjects will undergo leukapheresis within 14 days of screening.
Once successful manufacture of the WT1 TCR-transduced T cells has been confirmed by the Sponsor, each subject will be administered a lymphodepletive conditioning regimen for five days consisting of fludarabine x 5 days 30mg/m2 intravenous (i.v.) and methylprednisolone x 1 day 500 mg i.v. Upon completion of the conditioning regimen, subjects will receive an infusion of WT1 TCR-transduced T cells of ≤2 x 107/kg, followed by daily IL-2 subcutaneous injections (1 x 106 units/m2 subcutaneous (s.c.) od) for 5 days.
If an IWG response has not been reported (one or more criteria met) at 3 months post-infusion then, if agreed by both the Investigator and Sponsor, the subject will be offered to have a repeat infusion of WT1 TCR-transduced T cells.
Following infusion, subjects will enter an intensive period of out-patient follow-up to observe them for any acute complications and toxicities. Subjects will then be followed monthly in the clinic for the first 6 months for routine safety and clinical evaluations, including disease response evaluations. All subjects will be followed-up for a minimum of 12 months.
- Being tested
- Autologous WT1 TCR transduced T cells
- Keywords
- Gene Therapy, WT1 TCR, Gene modified T cels
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous WT1 TCR transduced T cellsGenetic
Gene therapy: Autologous WT1 TCR transduced T cells administered by intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Gene-modified WT1 TCR-transduced T cells | Experimental | A single dose of bulk WT1 TCR-transduced T cells (≤ 2 x 107/kg) will be intravenously (i.v.) administered following protocol-specified lymphodepletive conditioning regimen. Additionally, daily IL-2 subcutaneous injections (1x106 units/m2 subcutaneously (s.c.)) will be administered for 5 days concomitantly to each subject, following infusion of the ATIMP. Receives: Genetic: Autologous WT1 TCR transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety following gene-modified WT1 TCR T cell therapy as measured by suspected unexpected serious adverse reactions (SUSARS)
Measured: 12 Months
Proportion of subjects achieving one or more IWG response criteria following gene-modified WT1 TCR T cell therapy
Measured: 12 Months
Secondary outcomes (6)
Safety and tolerability of gene-modified WT1 TCR therapy as measured by clinical laboratory parameters and adverse events
Measured: 12 Months
Efficacy of WT1 TCR therapy as measured by haematological improvement, overall remission rate, marrow remission, cytogenetic response, molecular response, stable disease, AML transformation, progression free, event free and overall survival
Haematologic Response (peripheral blood): Haematological response will be assessed by haematology results and capturing data on number of RBC/platelet transfusions given to the subject.
Marrow Response: Bone marrow aspirate and/or biopsy morphology results will be recorded and assessed for marrow response in combination with peripheral blood response Cytogenetic response: cytogenetic evaluations will be performed on bone marrow aspirates/biopsies obtained during the trial.
Molecular response: molecular profile evaluations will be performed on bone marrow aspirates/biopsies obtained during the trial.
Disease response: Investigator will determine response (CR, PR, stable disease (SD), PD/TF) to administration of WT1 transduced T cells based on bone marrow blast count and peripheral blood assessments.
Subject disease events, progression and survival will be reviewed, assessed and recorded by the Investigator.
Measured: 12 Months
Technical feasibility of gene-modified WT1 TCR therapy in subjects with Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukaemia (AML).
Measured: 12 Months
Persistence of WT1 TCR-transduced T cells
Persistence of infused WT1 TCR-transduced T cells by Vβ2.1 and tetramer staining and PCR for Vβ2.1 and TCR-vector fragments.
Measured: 12 Months
Functionality and phenotype of WT1 TCR-transduced T cells
Function will be evaluated by measuring antigen-specific intracellular cytokine production in response to target cells that express HLA-A*201 alleles as well as WT1. Surface differentiation and memory phenotype will be determined using multi-parameter flow cytometry.
Measured: 12 Months
WT1 Transcript analysis in AML/MDS cells
WT1 overexpression will be used as a measure of disease monitoring on peripheral blood and BMA samples. RT-qPCR will be used to detect WT1 transcripts.
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study startSep 2015
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic Syndromes (MDS)Studies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cell Medica Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University College, London, Cell Therapy Catapult
- Responsible party
- Sponsor
- Investigators
- Emma Morris, MD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02550535
- Sponsor's protocol ID
- D-00272-CT2014002
- Status last verified
- Oct 2018
- First submitted
- 28 Apr 2015
- Last updated
- 2 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Phase I/II Study of the Safety and Efficacy of Gene-modified WT1 TCR Therapy in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukaemia (AML) Who Have Failed to Achieve or Maintain an IWG Response Following Hypomethylating Agent Therapy
- ClinicalTrials.gov ID
- NCT02550535
- Acronym / sponsor ID
- D-00272-CT2014002
- Keywords
- Gene Therapy, WT1 TCR, Gene modified T cels
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Cell Medica LtdIndustry (pharma, biotech, devices)
- Collaborators
- University College, London, Cell Therapy Catapult
- Study start
- Sep 2015
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 15 Sep 2015 (estimated)
- 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.
This is a Phase I/II trial to determine safety, clinical efficacy and feasibility of a gene-modified WT1 TCR therapy in patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML).
Patient's white blood cells (T cells) will be modified by transferring a gene which enables them to make a new T cell receptor (TCR) that can recognize fragments of a protein called WT1 (Wilms' tumour 1) which is present at abnormally high levels on the surface of myelodysplastic and leukaemic cells.
In this trial, approximately 25 participants with an Human Leukocyte Antigen A2 (HLA-A*0201) tissue type who have failed to achieve or maintain an IWG defined response following hypomethylating agent therapy will be recruited.
Detailed description
This is a Phase I/II trial to determine safety, clinical efficacy and feasibility of a gene-modified WT1 TCR therapy. Following provision of informed consent, each subject will undergo screening assessments, including HLA-A*0201 screening (if not already documented) and a bone marrow aspirate/biopsy (BMA) to determine subject eligibility for the trial.
Subjects will undergo leukapheresis within 14 days of screening.
Once successful manufacture of the WT1 TCR-transduced T cells has been confirmed by the Sponsor, each subject will be administered a lymphodepletive conditioning regimen for five days consisting of fludarabine x 5 days 30mg/m2 intravenous (i.v.) and methylprednisolone x 1 day 500 mg i.v. Upon completion of the conditioning regimen, subjects will receive an infusion of WT1 TCR-transduced T cells of ≤2 x 107/kg, followed by daily IL-2 subcutaneous injections (1 x 106 units/m2 subcutaneous (s.c.) od) for 5 days.
If an IWG response has not been reported (one or more criteria met) at 3 months post-infusion then, if agreed by both the Investigator and Sponsor, the subject will be offered to have a repeat infusion of WT1 TCR-transduced T cells.
Following infusion, subjects will enter an intensive period of out-patient follow-up to observe them for any acute complications and toxicities. Subjects will then be followed monthly in the clinic for the first 6 months for routine safety and clinical evaluations, including disease response evaluations. All subjects will be followed-up for a minimum of 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gene-modified WT1 TCR-transduced T cells | Experimental | Genetic: Autologous WT1 TCR transduced T cellsA single dose of bulk WT1 TCR-transduced T cells (≤ 2 x 107/kg) will be intravenously (i.v.) administered following protocol-specified lymphodepletive conditioning regimen. Additionally, daily IL-2 subcutaneous injections (1x106 units/m2 subcutaneously (s.c.)) will be administered for 5 days concomitantly to each subject, following infusion of the ATIMP. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- The trial will recruit subjects with MDS or AML who have received hypomethylating agent therapy (at least 6 cycles of azacitidine or 4 cycles of decitabine), and are EITHER:
- Relapsed, defined as failing to maintain an initial IWG response
- OR
- Stable, defined as failing to achieve an IWG response
- Subjects who have received hypomethylating agent therapy as part of a combination regimen may be eligible after discussion with the Sponsor.
Key exclusion criteria (12 listed)
- improvement or molecular response following azacitidine treatment
- CMML patients who have a white blood cell count > 13 x 109/L
- Acute promyelocytic leukaemia (FAB M3 Classification)
- Uncontrolled intercurrent illness
- Active malignancy, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
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 |
|---|---|---|
| Autologous WT1 TCR transduced T cellsGene therapy: Autologous WT1 TCR transduced T cells administered by intravenous infusion | Genetic | Gene-modified WT1 TCR-transduced T cells |
Primary outcome
Safety following gene-modified WT1 TCR T cell therapy as measured by suspected unexpected serious adverse reactions (SUSARS)
Time frame: 12 Months
Proportion of subjects achieving one or more IWG response criteria following gene-modified WT1 TCR T cell therapy
Time frame: 12 Months
6 secondary outcomes
Safety and tolerability of gene-modified WT1 TCR therapy as measured by clinical laboratory parameters and adverse events
Time frame: 12 Months
Efficacy of WT1 TCR therapy as measured by haematological improvement, overall remission rate, marrow remission, cytogenetic response, molecular response, stable disease, AML transformation, progression free, event free and overall survival
Time frame: 12 Months
Technical feasibility of gene-modified WT1 TCR therapy in subjects with Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukaemia (AML).
Time frame: 12 Months
Persistence of WT1 TCR-transduced T cells
Time frame: 12 Months
Functionality and phenotype of WT1 TCR-transduced T cells
Time frame: 12 Months
WT1 Transcript analysis in AML/MDS cells
Time frame: 12 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
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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.
Emma Morris, MD principal investigator
University College London Hospitals
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous WT1 TCR transduced T cells in people with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukaemia (AML), run by Cell Medica Ltd at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. 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: finished, as of the sponsor's last update on 2 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom, Belgium, Germany. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety following gene-modified WT1 TCR T cell therapy as measured by suspected unexpected serious adverse reactions (SUSARS) (time frame: 12 Months). The study lists 2 primary outcomes in all. 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 2 Oct 2018.