Study on Trametinib, Dexamethasone, Cyclophosphamide, and Cytarabine for Children with Relapsed or Refractory Blood Cancer

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What is this study about?

This clinical trial is focused on studying certain types of blood cancers in children, specifically Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma, which can be either in relapse or resistant to treatment. The study aims to explore the effects of a combination of medications, including Trametinib, Dexamethasone, Cyclophosphamide, and Cytarabine. These medications are being tested to see how safe they are and how well they work in treating these cancers.

The trial is divided into two phases. In the first phase, the focus is on determining the safest dose of the medications that can be given to patients. The second phase aims to evaluate how effective these medications are in treating patients with specific genetic changes in their cancer cells. The study involves taking these medications in different forms, such as tablets or injections, over a period of time. Some patients may receive a placebo, which is a substance with no active medication, to compare the effects.

Throughout the study, the health and progress of the participants will be closely monitored. This includes regular check-ups and tests to assess how the body is responding to the treatment. The goal is to gather information that could lead to better treatment options for children with these challenging types of blood cancer. The study is expected to continue until 2030, with the hope of providing valuable insights into the treatment of these diseases.

1 initial assessment

Upon joining the study, an initial assessment is conducted to evaluate eligibility. This includes reviewing medical history and performing necessary tests to confirm the presence of specific genetic mutations related to the condition.

2 treatment phase I

The first phase of treatment focuses on determining the maximum tolerated dose of the medications. This involves administering the drugs in increasing doses while monitoring for any side effects.

Medications include dexamethasone (oral tablets), methotrexate (injected into the spinal fluid), dexamethasone sodium phosphate (intravenous), cyclophosphamide (intravenous infusion), and cytarabine (intravenous infusion).

3 treatment phase II

In the second phase, the focus shifts to evaluating the effectiveness of the treatment. The medications are administered at the doses determined in Phase I.

Additional medications include hydrocortisone (injected into the spinal fluid), prednisolone sodium succinate (injected into the spinal fluid), and trametinib (oral tablets).

4 monitoring and follow-up

Throughout the trial, regular monitoring is conducted to assess the response to treatment and any side effects. This includes blood tests, imaging studies, and other evaluations as needed.

The primary goal is to determine the best overall response rate and monitor for any potential relapses or complications.

5 end of treatment

At the conclusion of the treatment period, a final assessment is performed to evaluate the overall outcomes and any long-term effects of the treatment.

Patients may be considered for further treatment options, such as stem cell transplantation, based on their response to the trial.

Who Can Join the Study?

Children must be between 1 year (at least 12 months) and 18 years old at the time of first diagnosis and less than 21 years old at the time of joining the study. They must be able to swallow tablets. Children under 6 years old must weigh at least 26 kg, and those over 6 years old must weigh at least 33 kg.
Children must have a certain level of activity or energy, measured by a score called the Karnofsky performance status (for those over 12 years old) or the Lansky Play score (for those 12 years old or younger). The score must be at least 50%.
Written permission must be given by the parents or legal representative, the patient, and the patient if they are old enough to understand, before any study-related tests are done. This must follow local, regional, or national rules.
Patients must have had tests called molecular profiling and flow-cytometric analysis on their disease before joining the study. These tests help understand the disease better. Other tests are recommended but not required. If these tests were done at the first diagnosis but not at relapse or when the disease returns, the patient might still join after discussing with the study organizers.
Patients must have specific changes in their tumor called RAS pathway activating mutations. These include changes in genes like KRAS, NRAS, HRAS, FLT3, PTPN11, MAP2K1, MP2K1, cCBL, and NF1, as found by molecular profiling.
Patients must have organs that work well enough. This includes:
- Kidney and liver function: Tests must show that the kidneys and liver are working within certain limits. For example, serum creatinine must be within 1.5 times the normal limit for age, and other liver tests must be within certain limits. If liver problems are due to the disease, the patient might still join after discussing with the study organizers.
- Heart function: The heart must be working well, shown by tests like echocardiography or MUGA. The heart’s shortening fraction must be more than 29% (or more than 35% for children under 3 years), and the left ventricular ejection fraction must be at least 50%. There should be no significant heart rhythm problems.

Who Cannot Join the Study?

Patients who have a different type of cancer than the ones being studied cannot participate.
Patients who are not in the age range specified for the study cannot participate.
Patients who are not able to follow the study procedures or instructions cannot participate.
Patients who have other serious health conditions that might interfere with the study cannot participate.
Patients who are pregnant or breastfeeding cannot participate.
Patients who have had a recent major surgery or are recovering from one cannot participate.
Patients who are currently participating in another clinical trial cannot participate.
Patients who have allergies to the study drugs or their ingredients cannot participate.
Patients who have a history of certain heart problems cannot participate.
Patients who have an active infection that requires treatment cannot participate.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Oslo Universitetssykehus HF	Oslo	Norway
Hospital Universitario Y Politecnico La Fe	Valencia	Spain
Centre Hospitalier Universitaire De Lille	Lille	France
Centre Hospitalier Universitaire De Bordeaux	Bordeaux	France

Other Sites

Site Name	City	Country
Prinses Maxima Centrum voor Kinderoncologie B.V.	Utrecht	The Netherlands
IRCCS Istituto Giannina Gaslini	Genoa	Italy
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain
St. Anna Kinderspital GmbH	Vienna	Austria
Fondazione IRCCS San Gerardo Dei Tintori	Monza	Italy
Ospedale Pediatrico Bambino Gesu’	Rome	Italy
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Centre Hospitalier Universitaire De Nantes	Nantes	France
Rigshospitalet	Copenhagen	Denmark
Azienda Ospedaliera di Padova	Padua	Italy
Karolinska University Hospital	Solna	Sweden
Centre Hospitalier Lyon Sud	Pierre Benite	France
Hopital Beaujon	Clichy	France
Uuujckpladwscobofumgh Ekppf Arg	Essen	Germany
Ueyfploydjqnfpwoeaihu Asmvdhym	Augsburg	Germany
Axtngltvjb Pprdqwgn Hkyzisif Dm Muucytsej	Marseille	France
Hejcjcvs Umtgafovxe Cahyewz Hitdsnia	Helsinki	Finland
Atbswhh Ovawccvzftk Ugytrunrjedfn Ceuuapbdlkbz Dwzrd Syjbim E Dfkud Subfnsr Dm Trbwex	Turin	Italy
Gpwmyv Uzcudcrfgd Fmuwwbhun	Frankfurt	Germany
Uaxkvwrlkhtsedhfghgtf Mjfxrqva Alk	Munster	Germany
Hwomuihy Vmrw doyukvvr	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Austria	Recruiting	01.07.2023
Belgium	Recruiting	01.07.2023
Denmark	Recruiting	01.07.2023
Finland	Not yet recruiting	01.07.2023
France	Not yet recruiting	01.07.2023
Germany	Recruiting	01.07.2023
Italy	Not yet recruiting	01.07.2023
Norway	Recruiting	01.07.2023
Spain	Recruiting	01.07.2023
Sweden	Recruiting	01.07.2023
The Netherlands	Recruiting	01.07.2023

Trial locations

Investigated drugs:

Trametinib

Investigational Agents are new drugs being tested in this trial to see if they are safe and how well they work for children with certain blood cancers that have come back or are not responding to treatment. These agents are designed to target specific changes in the cancer cells. The trial aims to find out the best dose that can be given safely and to see if these drugs can help treat the cancer effectively.

Acute Lymphoblastic Leukemia, in Relapse – This is a type of cancer that affects the blood and bone marrow, characterized by the overproduction of immature white blood cells called lymphoblasts. In relapse, the disease returns after a period of improvement or remission. The progression involves the rapid multiplication of these abnormal cells, which can crowd out normal cells, leading to symptoms like fatigue, fever, and increased risk of infections.

Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukemia) Recurrent – This is a cancer that originates from immature B-lymphocytes, a type of white blood cell. In its recurrent form, the disease returns after treatment. It typically presents as a mass in lymphoid tissues and can spread to other parts of the body, affecting the normal function of organs and tissues.

Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukemia) Recurrent – This disease involves the abnormal growth of immature T-lymphocytes. When recurrent, it means the disease has returned after initial treatment. It often presents with a mass in the chest and can spread to other areas, disrupting normal bodily functions.

Lymphoblastic Lymphoma (Precursor B-Lymphoblastic Lymphoma/Leukemia) Refractory – This condition involves cancerous growth of immature B-lymphocytes that does not respond to standard treatments. The disease can cause the formation of tumors in lymphoid tissues and may spread to other parts of the body, leading to various symptoms and complications.

Lymphoblastic Lymphoma (Precursor T-Lymphoblastic Lymphoma/Leukemia) Refractory – This is a type of cancer involving immature T-lymphocytes that fails to respond to conventional therapies. It often presents with a mass in the chest and can spread to other areas, causing a range of symptoms and affecting the function of different organs.

Trial ID:

2022-501869-41-00

Protocol code:

HEM-iSMART sub-D

NCT ID:

NCT05658640

Trial Phase:

Human Pharmacology (Phase I) – Other

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Study on Trametinib, Dexamethasone, Cyclophosphamide, and Cytarabine for Children with Relapsed or Refractory Blood Cancer

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?