Acute lymphoblastic leukaemia and lymphoblastic lymphoma MedDRA version: 18.1 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 18.1 Level: LLT Classification code 10065923 Term: Lymphoblastic lymphoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Dexamethasone
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 2-
P
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: The trial is open to all patients from age 1 (first birthday) to age 24 years 364 days (at time of diagnosis) with a first diagnosis of acute lymphoblastic leukaemia or lymphoblastic lymphoma (T-NHL or SmIg negative precursor B-NHL) diagnosed using standard criteria. Written informed consent is required for all patients and a negative pregnancy test for female patients of childbearing potential within 2 weeks prior to starting treatment. Are the trial subjects under 18? yes Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 111 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Trial entry and R1: 1)Infants less than a year old at diagnosis. 2)Patients with B-ALL (Burkitt-like, t(8;14), L3 morphology, SmIg positive) 3)Patients with Philadelphia-positive ALL (t(9;22) or BCR/ABL positive) 4)Patients in whom informed consent has not been obtained from parents and/or patients prior to randomisation 5)Patients who have received prior therapy for ALL or LBL except the following: a) Patients that have received a single dose of intrathecal methotrexate at the time of diagnostic LP b) patients with ALL who due to clinical urgency have received glucocorticoid (dexamethasone or prednisolone) for no more than 7 days c) patients with NHL or lymphomatous presentation of T-ALL who due to concerns over respiratory compromise or thoracic outlet obstruction have received emergency cytoreduction with glucocorticoid (dexamethasone or prednisolone) for no more than 7 days and/or up to 300mg/m2 cyclophosphamide in the previous 7 days. 6)Patients who are sexually active and are unwilling to use adequate contraception during therapy and for one month after last trial treatment. The following patients are excluded from the methotrexate and pulses randomisation (R2): 1) MRD High Risk ALL patients and LBL patients with a poor response at the end of induction (<35% reduction in tumour volume) 2) Any patients with significant renal impairment, pleural effusions or ascites. 3) Previous history of methotrexate encephalopathy. 4) MRD Intermediate patients with a history of pancreatitis. 5) Candidates for allogeneic SCT in CR1. 6) Down's syndrome patients 7) Patients who have received prior cranial irradiation 8) Patients with M3 marrow at day 29.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The UKALL 2011 trial will examine whether three changes to current standard therapy improves survival and reduces side effects in patients suffering from acute lymphoblastic leukaemia and lymphoblastic lymphoma. The following questions will be answered: 1) Does exposure to the steroid dexamethasone for a shorter period but at a similar total dosage than is currently used during the first month of treatment, result in fewer side effects whilst maintaining efficacy of treatment. 2) Does the use of methotrexate in high dose, reduce risk of relapse involving the central nervous system. 3) Is it possible to omit monthly pulses of vincristine and dexamethasone, currently given for up to 30 months, without increasing the risk of relapse, thereby reducing side effects and improving health related quality of life.;Secondary Objective: The secondary objective of the UKALL 2011 trial is provision of a platform for biological studies designed to improve future therapy for ALL and LBL. This is a further step toward the ultimate goal of individualised therapy in which the toxicity of treatment is balanced against the risk of relapse for each patient. Five biological studies are planned. Two of these will provide better information about prognosis – analysis of leukaemia cell genetics and development of a new method for detection of low levels of leukaemia known as flow MRD, during treatment. The remaining three studies will realise greater understanding of inter-individual variation in the behaviour of three important drugs – Dexamethasone, Asparaginase and Mercaptopurine. ;Primary end point(s): Dexamethasone randomisation (R1): Induction steroid-induced morbidity, defined as all serious adverse events and grade 3 or 4 adverse events related to induction and categorised as steroid related or steroid contributory. Methotrexate Randomisation (R2): Central Nervous System (CNS) relapse, defined as any relapse with CNS involvement, including combined. Pulses Randomi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Remission rate. Event free survival, overall survival, treatment related mortality. Morbidity and quality of life. ;Timepoint(s) of evaluation of this end point: Rate of remission is measured at the end of induction (4 weeks). Event free survival, overall survival, and treatment related mortality are evaluated up to 5 years. Morbidity will be assessed at the end of treatment (2 years for girls, 3 for boys). Quality of life is assessed at baseline, end of induction, end of interim maintenance, at 18 months, and at end of treatment in all patients. | — |
Countries
Ireland, United Kingdom
Outcome results
None listed