RecruitingRare disease

Study of TdT-3 cell therapy safety in patients aged 1 year and older with relapsed or refractory acute leukemia or lymphoblastic lymphoma

Verified siteInvestigationalNo placebo

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial studies the use of TdT-3, a special type of cell therapy that uses a patient's own modified immune cells, in treating acute lymphoblastic leukemia or lymphoblastic lymphoma. These are serious blood cancers that have not responded to standard treatments or have returned after previous treatment. The therapy involves taking the patient's own T-cells (a type of immune cell), modifying them in a laboratory to better recognize and fight cancer cells, and then returning them to the patient through an infusion into the bloodstream.

The purpose of this study is to test the safety of TdT-3 treatment and determine the most appropriate dose to use in future studies. Before receiving the cell therapy, patients will be given two medications called Fludarabine and Cyclophosphamide to prepare their body for the treatment. The treatment involves collecting the patient's blood cells through a procedure called leukapheresis, processing these cells in a laboratory to create the TdT-3 therapy, and then giving the modified cells back to the patient.

During the study, doctors will closely monitor patients for any side effects and check how well the treatment works. They will take blood samples and perform various tests to track the modified cells in the body and measure the patient's response to the treatment. The study will also look at how long the beneficial effects of the treatment last and whether patients can proceed to other treatments like stem cell transplantation if needed.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initial blood collection
Your blood cells will be collected through a procedure called leukapheresis. This requires having at least 150 T-cells per microliter in your blood.
A pregnancy test will be performed within 24 hours before the procedure if applicable.
Step 2
Preparation period
Your collected cells will be processed in a laboratory to create the TdT-3 treatment.
During this time, your health status will be monitored to ensure you are ready for the next phase.
Step 3
Pre-treatment conditioning
You will receive two medications: Fludarabine and Cyclophosphamide to prepare your body for the treatment.
A pregnancy test will be performed before starting this phase if applicable.
Step 4
TdT-3 treatment
The TdT-3 treatment will be given through an infusion into your vein.
The dose will be given in separate portions (fractionated doses) to ensure safety.
Step 5
Monitoring period
You will be monitored for 28 days after the treatment to check for any side effects.
Regular tests will be performed to measure the treatment's effectiveness.
Blood and bone marrow samples will be collected to track the TdT-3 cells in your body.
Your quality of life will be assessed through questionnaires at day 28.
Step 6
Long-term follow-up
Follow-up visits will occur at 3, 6, 9, 12, and 24 months after treatment.
These visits will include health assessments and quality of life questionnaires.
Your immune system recovery will be monitored during this period.

Who can join the trial?

17 criteria

Must be at least 1 year old at screening
Must have adequate T-cell recovery (at least 100 CD4+ T cells in blood) from previous therapy
For children under 6 years and first 3 patients: must have an identified stem cell donor
Must be able to undergo a blood filtering procedure called leukapheresis with at least 150 T cells per microliter of blood
If previously had stem cell transplant: must be at least 100 days since transplant and 30 days since last donor lymphocyte treatment
If previously had CAR T-cell therapy: must be at least 30 days since last treatment
Women who can become pregnant must have negative pregnancy test within 24 hours before key procedures
Must have life expectancy of at least 3 months
Must have suitable blood cells collected through leukapheresis for manufacturing treatment
Must have leukemia or lymphoma that has either not responded to standard treatments or no standard treatments are available
Cancer cells must show presence of TdT protein in testing
Must have specific genetic marker (HLA-A*02:01) and tumor cells must express HLA-A2
Must have measurable disease either in bone marrow or visible tumors on scans
Must provide written informed consent (parents/guardians for minors)
Must have adequate physical function score (Lansky or Karnofsky score ≥50)
Must have adequate kidney, liver, lung, and heart function based on medical tests
Must not have significant heart rhythm problems

Who cannot join the trial?

14 criteria

History of other types of cancer (except non-melanoma skin cancer) in the past 2 years
Active central nervous system (brain and spinal cord) involvement with leukemia
Uncontrolled infections that require intravenous antibiotics or antifungal medications
Severe heart conditions including:
- Heart failure with symptoms
- Unstable heart rhythm problems
- Recent heart attack (within 6 months)
- Severe liver problems with abnormal test results
- Severe kidney problems requiring dialysis
- Pregnancy or breastfeeding
- Known HIV infection (Human Immunodeficiency Virus)
- Active hepatitis B or C infection
- Previous treatment with similar cell therapy within the last 6 months
- Mental health conditions that could affect ability to understand or follow study requirements
- Any other serious medical condition that could make participation unsafe

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Oslo Universitetssykehus HF
Verified
Oslo, Norway

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Recruiting

Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

TdT-3
is an experimental cell therapy that uses a patient's own modified T-cells (a type of immune cell). The T-cells are genetically modified to recognize and target cells expressing TdT, which is found in certain types of leukemia and lymphoma. This is a personalized treatment where the patient's own immune cells are collected, modified in a laboratory, and then given back to the patient.
Fludarabine
is a chemotherapy medication used as part of the preparation treatment (conditioning) before receiving the cell therapy. It helps prepare the body by suppressing the immune system to help the modified T-cells work better.
Cyclophosphamide
is also a chemotherapy medication used alongside Fludarabine in the conditioning treatment. Like Fludarabine, it helps prepare the body for the cell therapy by suppressing the immune system and creating space for the new modified T-cells to grow.

What is already known about the treatment

TdT-3
An innovative autologous T-cell therapy where a patient's own T cells are genetically modified to express T-cell receptors (TCR) targeting Terminal deoxynucleotidyl Transferase (TdT) in cancer cells. This treatment is administered intravenously following conditioning with Fludarabine and Cyclophosphamide, and is currently being investigated in clinical trials for patients with relapsed or refractory TdT-positive acute leukemia or lymphoblastic lymphoma who are HLA-A*02:01 positive. The therapy belongs to the class of cellular immunotherapies, working by enabling modified T cells to recognize and eliminate cancer cells expressing the TdT protein.
Fludarabine
A chemotherapy medication administered intravenously as part of a conditioning regimen before cell therapy, typically used in combination with other drugs. This antimetabolite drug works by interfering with DNA synthesis in cancer cells and suppressing the immune system to prepare for cell therapy. It belongs to the class of purine analogs and is commonly used in the treatment of blood cancers and as part of preparation protocols for cellular therapies.
Cyclophosphamide
An alkylating chemotherapy agent given intravenously as part of conditioning treatment before cell therapy. This medication works by damaging the DNA of rapidly dividing cells and suppressing the immune system, making it effective both as a cancer treatment and as preparation for cell therapy. It belongs to the nitrogen mustard class of drugs and is widely used in various cancer treatments and as a conditioning agent for cellular therapies.

Investigated diseases

Acute lymphoblastic leukemia (ALL)
A type of blood cancer that affects white blood cells called lymphocytes in the bone marrow. The disease develops when young lymphocytes grow too quickly and don't mature properly, leading to an accumulation of immature cells. These abnormal cells crowd out healthy blood cells in the bone marrow and can spread to other parts of the body. The condition typically develops quickly, over days or weeks.
Lymphoblastic lymphoma (LBL)
A rare cancer that develops from immature lymphocytes, similar to ALL, but primarily affects lymph nodes and other tissues rather than the bone marrow. The disease causes lymph nodes to become enlarged as abnormal lymphocytes accumulate within them. It can also affect other organs such as the spleen, liver, and sometimes the skin. The condition shares many biological features with ALL but manifests differently in the body.