Treatment of Children With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Titre officiel

Treatment of Acute Lymphoblastic Leukemia in Children

Sommaire:

Cette étude vise à trouver de nouvelles façons de réduire les effets secondaires du traitement contre la leucémie et d’accroître le taux de guérison associé à cette maladie.

Durant cette étude, les recherches menées auront pour but :

  • de comparer les différences relatives à la toxicité, à l’efficacité et à la qualité de vie entre deux formes d’asparaginase (PEG-asparaginase et asparaginase dérivée d’E. coli);
  • de déterminer si l’administration d’un traitement plus énergique aux patients présentant un taux élevé de maladie résiduelle minimale permettra d’améliorer le taux de guérison de la maladie;
  • d’en apprendre davantage sur la biologie de la leucémie aiguë lymphoblastique en effectuant des recherches sur des échantillons de sang et de moelle osseuse;
  • de savoir comment le régime alimentaire peut influer sur le risque d’apparition d’effets secondaires associés à la chimiothérapie.

Description de l'essai

  • Determine event-free survival rates at 5 years
  • Determine asparaginase-related toxicity rates at the completion of 30 weeks of asparaginase therapy
  • Determine rate of infections at the end of a 32-day remission induction phase
  • Determine incidence of neurocognitive toxicities 5-years from diagnosis
  • Monitor quality of life measures during treatment

There are three different treatments being used in this study, which differ slightly in the types and amounts of chemotherapy drugs. Patients are assigned to different treatments based on features of their leukemia, such as their age, white blood cell count, and results of other tests. The three different groups are called "Standard Risk", "High Risk" and "Very High Risk". 

All treatment groups receive the following phases of therapy: Prophase, Induction, Consolidation I, central nervous system (CNS) therapy, Consolidation II and Continuation. Total treatment duration is 24 months from the date of complete remission. 

Research components of the protocol include the Asparaginase randomization, changing treatment based on minimal residual disease (MRD) testing, research blood and bone marrow specimens, quality of life questionnaires and dietary questionnaires. 

The Prophase consists of a three-day phase of oral or intravenous prednisone (day 1, 2 and 3) and intrathecal (in the spinal fluid) cytarabine (day 1). 

The Induction phase starts right after the Prophase. Patients in the "Standard Risk" group will receive: prednisone orally or intravenously (days 4-32); vincristine intravenously (days 4, 11, 18, and 25); doxorubicin intravenously (day 4 and 5); Methotrexate intravenously (day 6) and intrathecally (day 18 and 32); PEG asparaginase intravenously (day 8); hydrocortisone intrathecally (day 18); and cytarabine intrathecally (day 18). Patients in "High Risk" and "Very High Risk" groups will receive the above medication as well as dexrazoxane intravenously on days 4 and 5. 

At the end of the Induction phase blood tests, bone marrow biopsy and a spinal tap will be performed to determine whether or not the patient is in remission. 

The Consolidation I phase begins directly after the Induction phase. Patients in the "Standard Risk" group will receive; vincristine intravenously (day 1); 6-mercaptopurine orally (days 1-14); methotrexate intrathecally and intravenously (day 1); and leucovorin intravenously or orally (36 hours after methotrexate). Patients in the "High Risk" group receive the above medications as well as doxorubicin intravenously (day 1) and dexrazoxane intravenously (day 1). For patients in the "Very High Risk" group, the Consolidation phase is broken down into three sub-phases and involves the same drugs as the "High Risk" group with the addition of cyclophosphamide, cytarabine, etoposide, dexamethasone and asparaginase given at different time intervals.  

CNS therapy will begin after Consolidation therapy. Patients in the "Standard Risk" group will receive: Methotrexate/Cytarabine/Hydrocortisone intrathecally (twice weekly for 4 doses); vincristine intravenously (day 1); 6-mercaptopurine orally (days 1-14); dexamethasone orally (days 1-5); and asparaginase intravenously or intramuscularly by randomization (IM is 1 dose per week, IV is one dose every other week). Patients in "High Risk" and "Very High Risk" groups will receive the above drugs as well as doxorubicin intravenously (day 1) and dexrazoxane intravenously (day 1). 

During the CNS stage, some patients in the "High Risk" and all patients in the "Very High Risk" group will also receive radiation therapy in 8 or 10 daily treatments (total dose of 1200 or 1800 cGy, depending on whether or not there was leukemia in the spinal fluid at diagnosis). 

Consolidation II stage will begin after the CNS stage and consists of three-week cycles that last for 30 weeks. Patients in the "Standard Risk" group will receive: vincristine intravenously (day 1 of each cycle); 6-mercaptopurine orally (day 1-14 of each cycle); dexamethasone orally (days 1-5 of each cycle); asparaginase either intravenously or intramuscularly by randomization (IM is once per week, IV is once every other week); methotrexate intravenously or intramuscularly (one day after asparaginase); and methotrexate/cytarabine/hydrocortisone intrathecally (every 9 weeks for 6 doses than every 18 weeks). Patients in the "High Risk" or "Very High Risk" groups will receive the above treatment an in addition doxorubicin intravenously (day 1 of each cycle) and dexrazoxane intravenously (day 1 of each cycle). If a patient has received radiation, intrathecal medications are given less frequently. 

The Continuation phase begins after the completion of the Consolidation II phase. Patients will receive chemotherapy cycles every 3 weeks until they have been in remission for 2 years. All three groups receive the same treatment which consists of: vincristine intravenously (day 1 of each cycle); dexamethasone orally (day 1-5 of each cycle); 6-mercaptopurine orally (day 1-14 of each cycle); methotrexate intravenously or intramuscularly (weekly) and methotrexate/cytarabine/hydrocortisone intrathecally (every 18 weeks). 

The randomization of asparaginase involves PEG asparaginase (intravenously) and E. coli asparaginase (intramuscularly). PEG asparaginase will be given intravenously during the induction phase regardless of the randomization. Randomized treatment begins in the CNS therapy phase. The patients decision to take part in the randomization is separate from their decision to take part in the study as a whole. 

Minimal Residual Disease (MRD) testing will be performed at the end of the induction phase (day 32). It has been found that those children with higher levels of MRD in their bone marrow have a much higher chance of relapse than those children who have lower levels. The treatment will change for subjects with high MRD levels; these patients will be considered very high risk regardless of their initial risk group classification. 

Blood tests, urine tests, spinal taps and bone marrow tests will be collected throughout the study. 

Parents of all subjects will be asked to fill out a Quality of Life questionnaires about their child's health status. Patients, 12 years of age or oler, will be asked to complete their own forms. 

Parents will also fill out a questionnaire about the types of food the patient is eating. We hope to learn more about whether different types of food and vitamins affect the risk of developing side effects from chemotherapy. 

Voir cet essai sur ClinicalTrials.gov

Intéressé(e) par cet essai?

Imprimez cette page et apportez-la chez votre médecin pour discuter de votre admissibilité à cet essai et des options de traitement. Seul votre médecin peut vous recommander pour un essai clinique.

Ressources

Société canadienne du cancer

Ces ressources sont fournies en partenariat avec Société canadienne du cancer