|- candidate number||6021|
|- NTR Number||NTR1881|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||25-jun-2009|
|- Secondary IDs||Study ITCC 021 Innovative Therapies for Children with cancer|
|- Public Title||Bortezomib for children with acute lymphoblastic leukemia (ALL) without other treatment options.|
|- Scientific Title||Bortezomib (Velcade®): A feasibility and phase II study in childhood relapsed acute lymphoblastic leukemia.
|- ACRONYM||Bortezomib in relapsed ALL|
|- hypothesis||This is a phase II study of bortEzomib in combination with other chemotherapy as re-induction therapy for childhood relapsed/refractory ALL.|
|- Healt Condition(s) or Problem(s) studied||Acute Lymphoblastic Leukemia , Children, Relapse|
|- Inclusion criteria||1. Age between 6 months and 19 years;|
2. Patients with a second or subsequent relapsed ALL;
3. Patients with first relapsed ALL after prior allogeneic stem cell transplantation in first complete remission;
4. Patients with refractory first relapse of ALL, as defined by the ALL relapse protocol these patients were enrolled in;
5. Circulating leukemic blasts of at least 100/ul peripheral blood (i.e. at least 0.1x109/l);
6. Patients must take adequate contraceptives when of childbearing potential;
7. Written informed consent.
|- Exclusion criteria||1. Relapse not involving bone marrow;|
2. Symptomatic CNS leukemia;
3. Active uncontrolled infection;
4. Performance status (Lansky or Karnofsky score) of 60% or less;
5. Life expectancy of less than 6 weeks;
6. Existing peripheral neuropathy NCI grade 2 or higher;
7. Presence of acute diffuse infiltrative and/or pericardial disease;
8. Existing clinical signs of cardiotoxicity;
9. Previous allogeneic stem cell transplantation within 100 days;
10. Pregnant or breastfeeding;
11. Other contra-indications for chemotherapy, including no recovery from previous treatment;
12. Previous exposure to bortezomib;
13. Other experimental or conventional antileukemic treatment within 7 days from start of bortezomib;
14. Allergy to boron and its metabolites;
15. Concomitant anti-leukemic therapy other than according to this protocol.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-sep-2009|
|- planned closingdate||1-sep-2012|
|- Target number of participants||24|
|- Interventions||The patients will be treated with bortezomib (1.3 mg/m2/dose twice weekly (days 1 and 4 of each week) for a total of 2 weeks. Group A will get bortezomib on days 1, 4, 8 and 11, while group B will get it on days 8, 11, 15 and 18. Bortezomib will be administered as i.v. push. In addition, patients will get standard reinduction chemotherapy consisting of dexamethasone and vincristine. Dexamethasone will be given from day 1 onwards for 2 weeks at 10 mg/m2/day in 3 doses, orally. In addition, patients will receive vincristine on days 8 and 15, at 1.5 mg/m2/dose, in a 60 minutes i.v. infusion.
Finally, intrathecal methotrexate will be given on days 1 and 22 with age-adjusted dosing.
Further therapy for good responders (bone marrow (BM) M1 or M2 on day 22) may consist of an additional cycle of bortezomib, but this decision is left to the discretion of the treating physician. A next cycle should start 11 days after the previous administration of bortezomib. Then, bortezomib must again be combined with 2 weeks of dexamethasone (same dose and schedule) and vincristine twice (same dose and schedule). Such cycles may be repeated if justified by efficacy and (lack of) toxicity, which again is left to the discretion of the treating physician.
Patients with a BM M3 on day 22 and/or those with progressive disease will go off study.
|- Primary outcome||Determine the antileukemic activity of combination chemotherapy including bortezomib as reinduction therapy in childhood relapsed/refractory ALL.|
|- Secondary outcome||1. Determine the feasibility and safety of combining bortezomib with conventional combination chemotherapy in children and adolescents with relapsed/refractory ALL;|
2. Evaluate bortezomib levels and proteasome inhibition in cerebrospinal fluid, bone marrow and peripheral blood in patients with relapsed/refractory ALL, and assess the relationship to the efficacy and toxicity of bortezomib.
|- Timepoints||The major time point is the steroid response at day 8 and the response rate at day 22.|
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES|| C.M. Zwaan|
|- CONTACT for SCIENTIFIC QUERIES||Dr. Gertjan J.L. Kaspers|
|- Sponsor/Initiator ||Erasmus Medical Center|
(Source(s) of Monetary or Material Support)
|Stichting Kinderen Kankervrij, Nederland, Janssen Pharmaceutica|
|- Brief summary||Multicenter, multinational, open label, comparative and randomised phase II study on the antileukemic activity of bortezomib with conventional combination chemotherapy in relapsed/refractory ALL in children and adolescents. The study will include one cohort of patients with relapsed/refractory ALL, with treatment guidelines for all patients for 3 weeks. Thereafter, bortezomib may be repeated in combination with the same conventional chemotherapy for patients with a good initial response to reinduction therapy, while treatment of all other patients will be left at the discretion of the patient, parents and the responsible clinician. Standard reinduction chemotherapy will consist of 2 weeks of dexamethasone plus vincristine given twice, plus intrathecal administration of methotrexate. In addition, all patients will be treated with one cycle of bortezomib, consisting of 4 doses in 2 weeks. However, they will be randomised 1:1 in 2 arms, group A getting 'early' bortezomib, starting at day 1 of therapy, and group B getting 'late' bortezomib, starting at day 8. Randomisation will be stratified for the number of circulating leukemic blasts at diagnosis. This design allows demonstrating an additional antileukemic effect of bortezomib when added to dexamethasone, after 1 week of therapy, measured by a reduction in ALL cells in peripheral blood and bone marrow. In addition, this design allows comparing the toxicity of limited (group A) and more extended (group B) overlap of administrations of bortezomib and vincristine. A total of 24 patients must be randomised and be fully evaluable in order to prove additional antileukemic effect of bortezomib when added to dexamethasone. Bortezomib will be available for further use in case of patients with a favourable early treatment response, i.e. bone marrow M1 or M2 (ˇÜ15% blasts) 3 weeks after start of reinduction therapy, in combination with the same combination chemotherapy.|
|- Main changes (audit trail)||14-10-2013: |
- PLANNED CLOSINGDATE 31-jul-2014 , Prolonged patient inclusion period
|- RECORD||25-jun-2009 - 23-dec-2015|