HEM-iSMART-B: Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies
This study, called HEM-iSMART-B, is for children and young adults (aged 1-21) in the UK who have aggressive blood cancers like Acute Lymphoblastic Leukaemia (ALL) or Lymphoblastic Lymphoma (LBL). These are cancers that affect the blood-forming cells and lymph system, and they are either still present after treatment or have returned. The study is looking at a new combination of existing medicines: dasatinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine, along with intrathecal chemotherapy (chemo given directly into the fluid around the brain and spinal cord). The aim is to see if this combination is safe and effective for patients whose cancer has specific genetic changes, called 'alterations in the MAPK/SRC pathway'. By understanding these changes, doctors hope to offer more targeted and effective treatments.
At a glance
What is this study about?
The HEM-iSMART-B study is a clinical trial specifically designed for children and young adults (aged 1 to 21) who have aggressive blood cancers such as Acute Lymphoblastic Leukaemia (ALL) or Lymphoblastic Lymphoma (LBL). These are serious conditions where the body produces too many abnormal white blood cells. This study focuses on patients whose cancer has either come back after initial treatment (relapsed) or hasn't responded well to previous treatments (refractory). The goal is to find better ways to treat these difficult-to-treat cancers.
This study is part of a larger research programme called HEM-iSMART, which aims to develop more personalised treatments. For this specific 'Sub-protocol B' part of the study, researchers are testing a combination of several medicines: dasatinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine. They are also using intrathecal chemotherapy, which means giving chemotherapy directly into the fluid around the brain and spinal cord to reach cancer cells in those areas. The study is particularly interested in patients whose cancer cells have certain genetic changes, often called 'alterations' in the MAPK/SRC pathway. These genetic clues can help doctors understand which treatments might work best for an individual.
By carefully studying these new drug combinations in patients with specific genetic changes, doctors hope to gain important information about how safe these treatments are and how well they work. The ultimate aim is to improve the chances of successful treatment for children and young adults with these types of blood cancer, leading to better short-term and long-term health outcomes.
Key takeaways
- This study is for children and young adults (1-21) with certain types of aggressive blood cancer that have returned or not responded to previous treatments.
- It tests a new combination of existing medicines.
- Participation depends on specific genetic changes found in the cancer cells.
- The aim is to find safer and more effective treatments for these cancers.
- Patients will be closely monitored for safety and treatment effectiveness.
Who may be eligible?
This study is for children and young adults, specifically those aged between 1 and 18 years old at the time they were first diagnosed with cancer, and under 21 years old when they join the study. To be considered, patients must generally be well enough to take part in a clinical trial, as assessed by doctors.
Crucially, your doctors will need to have performed special tests on your cancer cells. These tests look for specific genetic changes, such as certain 'fusions' or 'amplifications' in genes like NUP214-ABL1, ABL1, or PDGFRβ. These genetic markers are key to whether a patient can join this particular study. If your cancer doesn't have these specific changes, this study may not be suitable for you.
If you are able to take medicines by mouth, you must be comfortable swallowing capsules, unless an oral liquid form is available. Importantly, your kidneys and liver need to be working well, and your heart must be healthy. These are standard checks to make sure the body can handle the study medications safely.
- Are you between 1 and 21 years old?
- Do you have Acute Lymphoblastic Leukaemia (ALL) or Lymphoblastic Lymphoma (LBL)?
- Has your cancer come back or not responded to previous treatments?
- Have your doctors found specific genetic changes (like NUP214-ABL1, ABL1, or PDGFRβ alterations) in your cancer cells?
- Are you generally well enough (good performance status) and do you have healthy kidney, liver, and heart function?
- Can you comfortably swallow capsules (if needed for oral medicines)?
This is a guide only — the research team will confirm whether you can take part.
What does participation involve?
If you decide to take part in this study, you will receive a new combination of medicines: dasatinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine. You will also have chemotherapy given directly into the fluid around your brain and spinal cord. The exact number of visits and the frequency will be explained by the study team, but you can expect regular appointments for blood tests, checks of your health, and to receive your medication.
Before you start, and at various points during the study, doctors will perform detailed evaluations, including repeating some of the special tests on your cancer cells to see how they are responding to the treatment. They will also keep a close eye on your general health, checking your organ functions like your kidneys and liver. The total duration of treatment and follow-up in the study will be clearly explained by the doctors, but it will involve a series of treatment cycles and ongoing monitoring.
Potential risks and benefits
Locations (33)
- St. Anna KinderspitalVienna, Austria· Not yet recruiting
- Universitair Ziekenhuis GentGhent, Belgium· Not yet recruiting
- Rigshospitalet CopenhagenCopenhagen, Denmark· Recruiting
- Helsinki University Hospital, New Children's HospitalHelsinki, Finland· Not yet recruiting
- Hôpital des Enfants GH Pellegrin - CHU de BordeauxBordeaux, France· Not yet recruiting
- CHRU Lille - Hôpital Jeanne de FlandreLille, France· Not yet recruiting
- Centre Léon BérardLyon, France· Not yet recruiting
- Hopital La Timone - EnfantsMarseille, France· Not yet recruiting
- CHU Nantes Hôpital Mère-EnfantNantes, France· Not yet recruiting
- Hôpital Robert DebréParis, France· Not yet recruiting
- Universitätsklinikum AugsburgAugsburg, Germany· Not yet recruiting
- Charité Universitätsmedizin BerlinBerlin, Germany· Not yet recruiting
+21 more sites — see the official record for the full list.
Common questions
What does 'relapsed' or 'refractory' mean?
It means the cancer has either come back after treatment, or it hasn't responded well to previous treatments.
What are 'genetic alterations' or 'changes in the MAPK/SRC pathway'?
These are specific changes within the cancer cells' DNA that can affect how the cancer grows. Doctors check for these to see if certain targeted treatments might work.
Are the medicines in this study new or commonly used?
Some of these medicines are already used for cancer, but their combination is being tested in a new way, especially for specific genetic changes in certain patients.
How long will I be in this study?
The exact duration will depend on various factors and will be discussed in detail by the study doctor. It involves treatment cycles and follow-up checks.
Will I still get regular cancer treatment if I join?
Yes, the study treatment is the regular cancer treatment you will receive while participating. You will be closely monitored by your medical team.
How to find out more
Anne Elsinghorst
Always speak to your GP or specialist before deciding to take part in a study.
Interested in taking part?
Discussion
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