New combo therapy offers hope for kids with tough leukemia

NCT ID NCT05658640

Disease control Sponsor: Princess Maxima Center for Pediatric Oncology Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jun 26, 2026

Summary

This study tests a new combination of drugs for children and young adults whose leukemia or lymphoma has returned or not responded to treatment. The drugs include trametinib (a targeted therapy) plus standard chemotherapy. The goal is to find the safest dose and see if the combination can shrink tumors or clear cancer cells from the bone marrow. About 26 participants will be enrolled.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Trametinib (a targeted cancer drug) combined with dexamethasone, cyclophosphamide, and cytarabine (chemotherapy drugs)
What this could lead to: If successful, this could offer a new treatment option for children with hard-to-treat leukemia or lymphoma that has come back or not responded to standard therapy.
What could go wrong: This is an early-phase trial with only 26 participants, so results may not apply to all patients. The drug combination may cause side effects or not work better than existing treatments.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1/2

Runs two stages together: safety and dose first, then whether the treatment works.

Participants

About 26 people

The number the study aims to enrol. It can still change while the study runs.

Started

Nov 2023

Expected to finish

Apr 2029

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

1 year to 21 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion criteria 1. Children between 1 year (≥ 12 months) and 18 years of age at the time of first diagnosis and less than 21 years at the time of inclusion. Patients under 6 years old must weigh at least 7 kg at the time of enrollment. Patients over 6 years old must weigh at least 10 kg at the time of enrollment. 2. Performance status: Karnofsky performance status (for patients \>12 years of age) or Lansky Play score (for patients * 12 years of age) ≥ 50% (Appendix I). 3. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study specific screening procedures are conducted, according to local, regional or national guidelines. 4. Patients must have had molecular profiling and flow-cytometric analysis of their recurrent or refractory disease at a time-point before the first inclusion into this trial (see section 9.1 of this protocol for detailed description of the molecular diagnostics required). Drug response profiling and methylation is highly recommended but not mandatory. Patients with molecular profiling at first diagnosis lacking molecular diagnostics at relapse or refractory disease may be allowed to be included after discussion with the sponsor. 5. Patients whose tumor present RAS pathway activating mutations including but not limited to KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1 hotspot mutations, cCBL; NF1 del, as detected by molecular profiling. 6. Adequate organ function: * RENAL AND HEPATIC FUNCTION (Assessed within 48 hours prior to C1D1) : * Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age or calculated creatinine clearance as per the Schwartz formula or radioisotope glomerular filtration rate ≥ 60 mL/min/1.73 m2. * Direct bilirubin ≤ 2 x ULN (≤ 3.0 × ULN for patients with Gilbert's syndrome). * Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤ 5 x ULN; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase/SGOT ≤ 5 x ULN. Note: Patients with hepatic disfunction related to the underling disease can be eligible even if they do not fulfill the aforementioned values for hepatic transaminases. In these cases, patients need to be discussed with the sponsor to confirm the eligibility. * CARDIAC FUNCTION: * Shortening fraction (SF) \>29% (\>35% for children \< 3 years) and/or left ventricular ejection fraction (LVEF) ≥50% at baseline, as determined by echocardiography or MUGA. * Absence of QTcF prolongation (QTc prolongation is defined as \>450 msec on baseline ECG, using the Fridericia correction), or other clinically significant ventricular or atrial arrhythmia. Exclusion Criteria 7. Pregnancy or positive pregnancy test (urine or serum) in females of childbearing potential. Pregnancy test must be performed within 7 days prior to C1D1. 8. Sexually active participants not willing to use highly effective contraceptive method (pearl index \<1) as defined in CTFG HMA 2020 (Appendix II) during trial participation and until 6 months after end of antileukemic therapy. 9. Breast feeding. 10. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome) in case of oral IMPs. 11. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including conventional chemotherapeutics (i.e. cytarabine and cyclophosphamide, intrathecal agents) and corticoids. 12. Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection. 13. Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion. 14. Subjects unwilling or unable to comply with the study procedures. 15. Previous treatment with trametinib. 16. Current use of a prohibited medication or herbal preparation or requires any of these medications during the study. See Section 7 and Appendix III for details. Drugs inducing QTc changes (prolongation of the QT interval or inducing Torsade de Points) are not permitted. 17. Unresolved toxicity greater than NCI CTCAE v 5.0 ≥ grade 2 from previous anti-cancer therapy, including major surgery, except those that in the opinion of the investigator are not clinically relevant given the known safety/toxicity profile of the study treatment (e.g., alopecia and/or peripheral neuropathy related to platinum or vinca alkaloid based chemotherapy) (Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov). 18. Active acute graft versus host disease (GvHD) of any grade or chronic GvHD of grade 2 or higher. Patients receiving any agent to treat or prevent GvHD post bone marrow transplant are not eligible for this trial. 19. Received immunosuppression post allogenic HSCT within one moth of study entry. 20. History or current evidence of retina vein occlusion (RVO) or central serous retinopathy are excluded. 21. Wash-out periods of prior medication: 1. CHEMOTHERAPY: At least 7 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea, 6-mercaptopurine, oral methotrexate and steroids which are permitted up until 48 hours prior to initiating protocol therapy. Patients may have received intrathecal therapy (IT) at any time prior to study entry. 2. RADIOTHERAPY: Radiotherapy (non-palliative) within 21 days prior to the first dose of drug. Palliative radiation in past 21 days is allowed. 3. HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Autologous HSCT within 2 months prior to the first study drug dose; Allogeneic HSCT within 3 months prior to the first study drug dose. 4. IMMUNOTHERAPY: At least 42 days must have elapsed after the completion of any type of immunotherapy other than monoclonal antibodies (e.g. CAR-T therapy) 5. MONOCLONAL ANTIBODIES AND INVESTIGATIONAL DRUGS: At least 21 days or 5 times the half-life (whichever is shorter) from prior treatment with monoclonal antibodies or any investigational drug under investigation must have elapsed before the first study drug. 6. SURGERY: Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery.

Get updates

Get notified about this study

Sign up to get updates when this study changes or when new studies for Acute lymphoblastic leukemia, in relapse are added.

Vår säkerhetsrekommendation!

Genom att skicka in godkänner du våra Användarvillkor

Conditions

The condition(s) this trial relates to.

acute lymphoblastic leukemia B-cell acute lymphoblastic leukemia leukemia Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Precursor Cell Lymphoblastic Leukemia-Lymphoma precursor lymphoblastic lymphoma/leukemia Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Recurrence refractory precursor T-lymphoblastic lymphoma/leukemia

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Acute lymphoblastic leukemia, in relapse Lymphoblastic lymphoma (precursor B-lymphoblastic lymphoma/leukaemia) recurrent Lymphoblastic lymphoma (precursor B-lymphoblastic lymphoma/leukaemia) refractory Lymphoblastic lymphoma (precursor T-lymphoblastic lymphoma/leukaemia) recurrent Lymphoblastic lymphoma (precursor T-lymphoblastic lymphoma/leukaemia) refractory

How to take part

Only the study team decides who joins. These are the ways to reach them.

The places running it

36 sites in 15 countries. The list below names each one and where it is.
The official record

ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.

Open the record ↗
A doctor treating you

A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.

Contacts and locations

Locations

Bristol Royal Hospital for Children
NOT_YET_RECRUITING

Bristol, B52 8BJ, United Kingdom
CHRU Lille - Hôpital Jeanne de Flandre
NOT_YET_RECRUITING

Lille, 59037, France
CHU Nantes Hôpital Mère-Enfant
NOT_YET_RECRUITING

Nantes, 44093, France
Centre Léon Bérard
NOT_YET_RECRUITING

Lyon, 69 373, France
Charité Universitätsmedizin Berlin
RECRUITING

Berlin, 13353, Germany
Fondazione MBBM c/o Centro ML Verga
NOT_YET_RECRUITING

Monza, 20900, Italy
Great North Children's Hospital
NOT_YET_RECRUITING

Newcastle, NE1 4LP, United Kingdom
Great Ormond Street Hospital for Children NHS Trust
NOT_YET_RECRUITING

London, WC1N 2BH, United Kingdom
Helsinki University Hospital, New Children's Hospital
NOT_YET_RECRUITING

Helsinki, FI00029, Finland
Hopital La Timone - Enfants
NOT_YET_RECRUITING

Marseille, 13005, France
Hospital Infantil Universitario Niño Jesús
NOT_YET_RECRUITING

Madrid, 28009, Spain
Hospital Sant Joan de Déu de Barcelona
NOT_YET_RECRUITING

Barcelona, 08950, Spain
Hospital Vall d'Hebron
NOT_YET_RECRUITING

Barcelona, 08035, Spain
Hôpital Robert Debré
NOT_YET_RECRUITING

Paris, 75019, France
Hôpital des Enfants GH Pellegrin - CHU de Bordeaux
NOT_YET_RECRUITING

Bordeaux, 33076, France
IRCCS Istituto Giannina Gaslini
NOT_YET_RECRUITING

Genova, 16147, Italy
Karolinska university hospital
RECRUITING

Stockholm, 171 76, Sweden
La Fe
NOT_YET_RECRUITING

Valencia, 46026, Spain
Oslo University Hospital
RECRUITING

Oslo, 0373, Norway
Ospedale Infantile Regina Margherita
NOT_YET_RECRUITING

Turin, 10126, Italy
Ospedale Pediatrico Bambino Gesù, IRCCS
NOT_YET_RECRUITING

Roma, 0165, Italy
Our Lady's Hospital for Sick Children
NOT_YET_RECRUITING

Dublin, D12N512, Ireland
Padova Azienda Ospedaliera
NOT_YET_RECRUITING

Padova, 35128, Italy
Princess Máxima Center for Pediatric Oncology
RECRUITING

Utrecht, Utrecht, 3584CS, Netherlands
Rigshospitalet Copenhagen
RECRUITING

Copenhagen, DK-2100, Denmark
Royal Manchester Children's Hospital
NOT_YET_RECRUITING

Manchester, M13 9WL, United Kingdom
Royal Marsden NHS Trust
NOT_YET_RECRUITING

Sutton, SM2 5PT, United Kingdom
Schneider's Children's Medical Center
NOT_YET_RECRUITING

Petah Tikva, 4920235, Israel
Sheba Medical Center Hospital
NOT_YET_RECRUITING

Ramat Gan, 52621, Israel
St. Anna Kinderspital
NOT_YET_RECRUITING

Vienna, 1090, Austria
Universitair Ziekenhuis Gent
NOT_YET_RECRUITING

Ghent, 9000, Belgium
University Children's Hospital Zürich
NOT_YET_RECRUITING

Zurich, CH-8032, Switzerland
Universitätsklinikum Augsburg
NOT_YET_RECRUITING

Augsburg, 86156, Germany
Universitätsklinikum Essen
NOT_YET_RECRUITING

Essen, 45147, Germany
Universitätsklinikum Frankfurt
NOT_YET_RECRUITING

Frankfurt, 60590, Germany
Universitätsklinikum Münster
NOT_YET_RECRUITING

Münster, 48149, Germany

More trials for these conditions

Other studies related to the condition(s) this trial covers.