| DEC-NET Serial number GB313 |
| |
| Published online | 24/08/2004 12.55.00 |
| Last updated | 28/02/2006 14.31.45 |
| |
| Other protocol ID number | Mrec No 02/9/21, NCRN trial ID 1347 |
| This trial has been approved by an ethics committee |
| Current trial status | Open (actively recruiting new participants) |
First subject enrolment
Target N. of subjects |
01/2003
200 |
Major Disease
(ICD9 class) | LYMPHOID LEUKEMIA ACUTE |
| Experimental drug |
Mitoxantrone
Treatment regimen (dosage and duration)
10mg/m2 phase I for 2 days |
IDARUBICIN
Treatment regimen (dosage and duration)
10m2 Phase I for 2 days |
METHOTREXATE
Treatment regimen (dosage and duration)
IT dose by age (<2y: 8mg, 2y: 10mg, >=3y: 12mg) Phase I for 2 days unless CNS disease present: once a week until two clear CSF samples are obtained. Phase II for 1 day, Phase III for 2 days, Phase V for 4 days, Phase VI for 1 day. IV 1000mg/m2 Phase II for 1 day, Phase III for 1 day. Oral 20mg/m2 once a week for 4 weeks in Phase V, Phase VI for 88 weeks, 100mg/m2 given as 25mg/m2 every 6 h for2 days |
CYCLOPHOSPHAMIDE
Treatment regimen (dosage and duration)
440mg/m2 in Phase II for 5 days, 300mg/m2 in Phase V for 4 days |
DEXAMETHASONE AND ANTIINFECTIVES
Treatment regimen (dosage and duration)
20mg/m2/day in Phase I for 10 days, 6mg/m2/day in Phase II for 5 days, Phase III for 5 days, Phase V for 10 days, Phase VI for 15 days |
Daunorubicin
Treatment regimen (dosage and duration)
N/A |
ETOPOSIDE
Treatment regimen (dosage and duration)
100mg/m2 in Phase II for 5 days, 150mg/m2 in Phase V for 4 days. |
Pegylated asparaginase
Treatment regimen (dosage and duration)
1000 units/m2 Phase I for 2 days, in Phase II for 1 day. |
MERCAPTOPURINE
Treatment regimen (dosage and duration)
75mg/m2 daily from weeks 14-19 and weeks 22-27 in Phase V, 75mg/m2 daily for 88 weeks in Phase VI. |
Fludarabine
Treatment regimen (dosage and duration)
Phase IV if applicable, 25mg/m2 for 5 days. |
Alemtuzumab
Treatment regimen (dosage and duration)
0.2 mg/kg for 5 days for those receiving fully matched unrelated donors, haplotype transplants with Campath serotherapy and mismatched unrelated donor Marrow transplants |
Cyclosporin
Treatment regimen (dosage and duration)
3mg/kg to be divided into 2 daily doses from day -1 for those who receive BMT |
| Gender | Both |
| Age (range) | 1<18 |
Eligibility criteria |
| Inclusion criteria |
| 1) Previously diagnosed to have acute lymhoblastic leukaemia and have either relapsed after treatment or have primary refractory disease
2) For children who have relapsed, only those in whom this is the first relapse are eligible
3) Provide signed written informed consent from parent and/or guardian
4) Protocol to have received national local ethical committee approval |
| Exclusion criteria |
| 1) Children in whom this is not the first relapse of their disease
2) Children with first relapse who have already received chemotherapy or radiotherapy prior to starting R3 |
Trial design/methodology |
| Phase | 2 |
| Kind of study | Efficacy
Safety
|
| Design | Randomised
|
| Purpose of study |
| The primary objective is to utilise a new chemotherapy approach for children with relapsed acute lymphoblastic leukaemia (ALL) based on risk group stratification and therapy directed by the presence of minimal residual disease. The aim is to standardise nationally the treatment of children with ALL who fail induction or relapse once morpholigical remission has been obtained. |
| Primary outcomes |
| The following end points will be used, stratisfied by risk group: death in continuous clinical remission, relapse, second malignancy. The MRD level of 10-4, will be used at the end of induction in the intermediate group to distinguish those who will benefit from chemotherapy or BMT |
| Secondary outcomes |
| Any relationship between MRD results and response to therapy |
| Summary of study design, objectives, and ongoing research findings |
| This is a randomised, open-label prospective clinical trial in children with relapsed acute lymphoblastic leukaemia. The trial risk stratisfies children with relapsed ALL into standard, intermediate and high risk based on time to relapse after the original diagnosis, immunophenotype (T or B cell) and site of relapse. all high risk children are being offered transplantation, and those with standard risk chemotherapy. an additional risk stratification is being performed in the intermediate risk group (70%) based on the response to therapy. This is being measured by identifying and quantifying clonotypic markers to the IgH and TCR loci in lymphoblasts. Intermediate risk children with residual of disease >10-4 after 5 weeks of treatment are re-classified as high risk and offered transplantation. Those with a lower level of disease are being offered chemotherapy. A randomisation is being performed at induction, between Idarubicin and Mitoxantrone with all patients being eligible for randomisation.
The study aims to improve the outcome in children with intermediate risk ALL, examine the role of Cytoreduction prior to bone marrow transplantarion to improve outcome and compare the results of UKALL R3 on a yearly basis with BFM REZ 2003 to show that outcome is comparable. |
