RecruitingPHASE1, PHASE2INTERVENTIONAL

HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies

This study, called HEM-iSMART-C, is for children and young adults (up to age 21) who have blood cancers like acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LBL) that have returned or are not responding to standard treatments. We are testing a combination of several existing medications: ruxolitinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine, along with intrathecal chemotherapy. The main goal is to see how safe and effective this new combination is, especially for patients whose cancer has specific changes in something called the IL7R/JAK-STAT pathway. By using a 'personalised medicine' approach, we hope to find better ways to treat these challenging cancers.

At a glance

Status

Recruiting

Phase

PHASE1, PHASE2

Sponsor

Princess Maxima Center for Pediatric Oncology

Enrolment target

Start

01 Oct 2025

Estimated completion

02 Feb 2032

Acute Lymphoblastic Leukemia, in Relapse Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Recurrent Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Recurrent Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukaemia) Refractory Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukaemia) Refractory

What is this study about?

The HEM-iSMART-C study is trying out a new way to treat certain blood cancers in children and young adults, specifically acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL). These are types of cancer that affect blood cells or the immune system. Sometimes, these cancers can return after treatment or not respond to the usual medicines. This study aims to find safer and more effective treatments for these situations.

Researchers have found that some of these cancers have specific tiny changes in their genes, almost like a unique fingerprint. This study focuses on cancers that have changes in a particular pathway called the IL7R/JAK-STAT pathway. By understanding these gene changes, doctors can choose medicines that are designed to target these specific changes more directly. This is often called 'personalised medicine' because the treatment is tailored to the individual's cancer.

In this study, doctors are combining several medications that are already used or being studied for cancer. These include ruxolitinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine. They will also use intrathecal chemotherapy, which is a way of giving medicine directly into the fluid around the brain and spinal cord. The study will carefully watch how safe this combination of medicines is and how well it works in shrinking the cancer or stopping it from growing. It's a two-part study (Phase 1/Phase 2): the first part focuses on safety and finding the right dose, and the second part looks at how well the treatment works.

Key takeaways

Targets specific blood cancers in children and young adults (up to 21).
Focuses on cancers with particular genetic changes (IL7R/JAK-STAT pathway).
Uses a combination of existing medicines and chemotherapy.
Aims to find safer and more effective treatment options.
Participation requires regular hospital visits and close monitoring.
You can withdraw from the study at any time.

Who may be eligible?

This study is looking for children and young adults aged between 1 and 21 years old. To join, you must have been diagnosed with acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LBL) that has either come back (relapsed) after previous treatment or is not responding (refractory) to current treatments.

A very important part of joining this study is that your cancer must show specific genetic changes. These changes are in something called the IL7R and/or JAK-STAT pathways. Doctors will need to do special tests on your cancer cells to confirm these changes. This helps ensure the treatment is targeted to your specific type of cancer.

Other requirements include having good overall health, as measured by your ability to do daily activities, and your organs (like kidneys and liver) must be working well. You also need a parent or legal guardian to give written permission for you to take part, and if you're old enough, you'll need to agree to participate too.

Quick self-check

Are you between 1 and 21 years old?
Do you have ALL or LBL that has come back or isn't responding to treatment?
Have your doctors confirmed specific genetic changes in your cancer (IL7R/JAK-STAT pathway)?
Are you generally well enough to take part in daily activities?
Do you have a parent/guardian who can give permission, and are you willing to agree yourself if old enough?

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 combination of medicines: ruxolitinib, venetoclax, dexamethasone, cyclophosphamide, and cytarabine. You will also receive chemotherapy directly into the fluid around your brain and spinal cord. The study will involve regular visits to the hospital for doctors to check your health, monitor for any side effects, and see how well the treatment is working.

These visits will include blood tests, physical examinations, and possibly other tests as needed. The exact number of visits and the total duration of your participation will depend on how you respond to the treatment and the stage of the study. The study aims to follow how you're doing over time to fully understand the effects of the medicines.

Potential risks and benefits

Taking part in this study may offer the potential benefit of accessing new combinations of medicines that could be more effective for your specific type of cancer, especially if standard treatments haven't worked well. However, all medicines have possible side effects, and these new combinations could have risks that aren't fully known yet. The study team will monitor you very closely for any side effects. You have the right to withdraw from the study at any time, for any reason, without it affecting your future medical care.

Locations (33)

St. Anna Kinderspital
Vienna, Austria· Not yet recruiting
Universitair Ziekenhuis Gent
Ghent, Belgium· Not yet recruiting
Rigshospitalet Copenhagen
Copenhagen, Denmark· Recruiting
Helsinki University Hospital, New Children's Hospital
Helsinki, Finland· Not yet recruiting
Hôpital des Enfants GH Pellegrin - CHU de Bordeaux
Bordeaux, France· Not yet recruiting
CHRU Lille - Hôpital Jeanne de Flandre
Lille, France· Not yet recruiting
Centre Léon Bérard
Lyon, France· Not yet recruiting
Hopital La Timone - Enfants
Marseille, France· Not yet recruiting
CHU Nantes Hôpital Mère-Enfant
Nantes, France· Not yet recruiting
Hôpital Robert Debré
Paris, France· Not yet recruiting
Universitätsklinikum Augsburg
Augsburg, Germany· Not yet recruiting
Charité Universitätsmedizin Berlin
Berlin, Germany· Recruiting

+21 more sites — see the official record for the full list.

Common questions

What kind of cancer is this study for?

This study is for children and young adults with acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma (LBL) that has returned or is not responding to treatment.

What are 'genetic changes' and why are they important for this study?

Genetic changes are tiny alterations in the cancer cells that can affect how they grow. This study is specifically for cancers with changes in the IL7R/JAK-STAT pathways, as the medicines are designed to target these changes.

Are the medicines new ones that no one has ever used?

Some of the medicines are already used for other conditions or being studied for cancer. This trial is combining them in a new way to see if they work better together for your specific cancer type.

Will I have to stay in the hospital for the whole study?

You will have regular hospital visits for treatment and checks, but you may not need to stay in the hospital for the entire duration of the study. Your medical team will explain the schedule.

Can I stop being in the study if I want to?

Yes, you can choose to leave the study at any time, for any reason. Your decision will not affect your future medical care.

How to find out more

Anne Elsinghorst

hem-ismart@prinsesmaximacentrum.nl +316 5000 6270 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.