Clinical trial · Interventional
A Phase I/II Study of Gene-modified WT1 TCR Therapy in MDS & AML Patients
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukaemia (AML) | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Myelodysplastic Syndromes (MDS) | Myelodysplastic Syndrome | ALIAS | 0.85 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Autologous WT1 TCR transduced T cells | Genetic | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Gene-modified WT1 TCR-transduced T cells
- description
- 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.
- interventionNames
- Genetic: Autologous WT1 TCR transduced T cells
Primary outcomes (2)
- measure
- Safety following gene-modified WT1 TCR T cell therapy as measured by suspected unexpected serious adverse reactions (SUSARS)
- timeFrame
- 12 Months
- measure
- Proportion of subjects achieving one or more IWG response criteria following gene-modified WT1 TCR T cell therapy
- timeFrame
- 12 Months
Secondary outcomes (6)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Key Inclusion criteria:
* 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.
1. Subjects aged 18 years or older who have a diagnosis of, EITHER:
* 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)
2. Subjects with documented HLA-A\*0201 positive serotype
3. Subjects with less than 30 per cent bone marrow blasts
4. Subjects with relapsed disease must have less than 5 per cent peripheral blasts
5. Subjects with stable disease must have less than 10 per cent peripheral blasts
6. Subjects with less than a doubling of bone marrow blast count between the start of hypomethylating agent therapy and the date of screening
7. 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.
8. Subjects with ECOG status 0, 1 or 2
9. Subjects who have at least one cytopenia (ANC \<1000/μL, platelet count \<75,000/μL, Hgb \<11g/dL or RBC transfusion dependence)
Key Exclusion criteria:
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
* 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)References
Publications (0)
Data not yet available