None listed
Conditions
Brief summary
Phase 3 This international trial investigates the use of multi-agent chemotherapy and radiotherapy in children with relapsed or resistant lymphoblastic leukaemia, based on early response as measured by minimal residual disease (MRD) levels, in order to improve treatment. Who is it for? You can join this study if you are aged 1–18 years and have been diagnosed with acute lymphoblastic leukaemia which has relapsed or does not respond to first-line treatment. Trial details Participants are treated with multi-agent chemotherapy and radiotherapy based on early response as measured by minimal residual disease (MRD) levels. (These are the low levels of cancer cells that remain in the body after treatment.) Regular sensitive testing is carried out on the bone marrow to measure how quickly the leukaemia is responding to treatment, and this information is used to help determine whether a transplant or more chemotherapy is a better option for each patient. For those children who show a particularly slow response to chemotherapy, extra intensive chemotherapy is used before transplant to try to improve the control of the leukaemia and improve the chance of cure. Any disease progression is monitored.
Interventions
multi-agent chemotherapy, based on early response as measured by minimal residual disease (MRD) levels
Phase I Induction (weeks 1-4):
Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3 yrs 12mg, on day 1,of week 1 and day 1 of Week 2.
Idarubicin or Mitoxantrone, 10mg/m2 intravenous (IV) over 1 hour, on days 1 and 2 of week 1.
Dexamethasone, 20mg/m2 orally in 2 divided doses per day (max 40mg/day), on days 1-5 of week 1 and days 1-5 of week 3.
Vincristine, 1.5mg/m2 iv bolus (max 2mg as a singl
multi-agent chemotherapy, based on early response as measured by minimal residual disease (MRD) levels Phase I Induction (weeks 1-4): Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3 yrs 12mg, on day 1,of week 1 and day 1 of Week 2. Idarubicin or Mitoxantrone, 10mg/m2 intravenous (IV) over 1 hour, on days 1 and 2 of week 1. Dexamethasone, 20mg/m2 orally in 2 divided doses per day (max 40mg/day), on days 1-5 of week 1 and days 1-5 of week 3. Vincristine, 1.5mg/m2 iv bolus (max 2mg as a single dose), on day 3, week 1, day 3 of week 2, day 3 of week 3, day 3 of week 4. Peg Asparaginase, 1000u/m2 intramuscular(im), on day 3 of week 1 and day 3 of week 3 OR Erwinase, 20,000units/m2 (im) on day 3 of week 1 and then alternate days for 12 doses in total. Phase II Consolidation (weeks 5-8): Dexamethasone, 6mg/m2 orally in 2 divided doses, on days 1-5 of week 5. Vincristine, 1.5mg/m2 (iv), Max 2mg as a single dose, on day 3 of week 5. Intrathecal Methotrexate, <2yrs 8mg; 2 yrs 10mg; >3 yrs 12mg, on day 1 of week 6 Methotrexate, 1000mg/m2 (iv) over 36 hours, on day 1 of week 6 Peg Asparaginase, 1000u/m2, (im) on day 2 of week 6, 4 hours after the end of methotrexate infusion. OR if allergic to E. Coli Asparaginase Erwinase, 20,000u/m2 (im), on day 2 of week 6, 4 hours after end of MTX infusion and then alternate days for 6 doses in total Cyclophosphamide, 440mg/m2 (iv) infusion over 30 minutes, on day 1-5 of week 7 Etoposide, 100mg/m2 (iv) over 4 hours, on days 1-5 of week 7. Phase III Intensification (weeks 9-13) Dexamethasone, 6mg/m2 orally in 2 divided doses, on days 1-5 of week 9. Vincristine, 1.5mg/m2 (iv), Max 2mg as a single dose, on day 3 of Week 9 Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3yrs 12mg, on day 1 of week 9. Cytarabine, 3000mg/m2 (iv) over 3 hours, every 12 hours, on day 1 and 2 of week 9 and day 1, 2 of week 10. Erwinase, 20,000u/m2 (im), on day 2 and day 4 of week 9 and on day 2 and day 4 of week 10. Prednisolone eye drops every 2 hours from day 1, week 9 and stopped 5 days after the last Cytarabine infusion. Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3yrs 12mg, on day 1 of week 12. Methotrexate, 1000mg/m2 (iv) over 36 hours, on day 1 of week 12 Erwinase 20,000u/m2 (im), on day 2 of week 12, 4hrs after the end of the Methotrexate infusion.
Sponsors
University Hospitals of Leicester National Health Service (NHS) Trust
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria: 1. All patients aged 1-18 years who have been previously diagnosed to have acute lymphoblastic leukaemia and have either relapsed after treatment or have primary refractory disease 2. Only those patients in whom this is the first relapse are eligible 3. Written, informed consent according to national guidelines 4. Appropriate ethical committee approval.
Exclusion criteria
Exclusion Criteria: 1. Those who have first relapse but have already received chemotherapy or radiotherapy for the relapse, prior to starting R3 2. Patients who have had a prior bone marrow transplant 3. Those with mature B-cell ALL
Outcome results
None listed