HEM-iSMART subprotocol D (ALL/LBL)

Recruiting

Who can enter

• Children with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who have had an inadequate response to previous treatment (refractory) or whose disease has come back (relapse), with changes in the RAS pathway

• Age: 1 to 21 years

Goal

The goal of this study is to investigate whether the drug trametinib is tolerable, safe and effective in combination with dexamethasone, cyclophosphamide and cytarabine. This is tested in patients who have had an inadequate response to previous treatment (refractory) or whose disease has come back (relapse).

Background

Certain changes (mutations) present in leukemia or lymphoma cells are responsible for increased and uncontrolled cell growth. Changes known to act like that are mutations in several genes called the "RAS signaling pathway." We refer to this as “RAS mutations”. Patients diagnosed with a RAS mutation are often more difficult to treat than patients without this mutation.

The drug trametinib inhibits these RAS mutations and can slow down or stop the growth of the cancer. In children in whom RAS mutations have been found in the cancer cells, we hope that trametinib will reduce the disease far enough to allow proceeding to stem cell transplantation.

Dexamethasone, cyclophosphamide and cytarabine are drugs that can cause leukemia and lymphoma cells to die more quickly. Laboratory studies on ALL cells have shown that the combination of trametinib with dexamethasone works better than either trametinib or dexamethasone alone (synergistic effect).

The study consists of two parts: a phase 1 and phase 2 part. Phase 1 will investigate which dose of the drug trametinib in combination with dexamethasone, cyclophosphamide and cytarabine is safe for patients who have had an incomplete response to previous treatment or who have had a recurrence of the disease. If the combination of these drugs turns out to be safe, it will move on to phase 2, in which is investigated whether the combination of drugs is effective against the disease.

In order to participate in this study please refer to your/your child’s doctor.
For international patients: please feel welcome to contact our International Patients Office.

Last reviewed

March 20, 2026

The above information is intended as a brief summary only and may not reflect the most up-to-date information. For full details and the current status of a protocol, physicians can contact the Princess Máxima Center directly.