|- candidate number||1226|
|- NTR Number||NTR136|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||23-aug-2005|
|- Secondary IDs||N/A |
|- Public Title||TRIAL Relapsed AML 2001/01.|
|- Scientific Title||A randomised phase III study on the treatment of children and adolescents with refractory or relapsed acute myeloid leukemia (AML).|
|- ACRONYM||Relapsed AML 2001/01|
|- hypothesis||Addition of liposomal daunorubicin (DaunoXomeŽ) to FLAG in the first reinduction course will result in improved treatment response with acceptable toxicity and without increased cardiotoxicity.|
|- Healt Condition(s) or Problem(s) studied||Acute Myeloid Leukemia (AML)|
|- Inclusion criteria||1. Primary refractory AML;
2. First relapsed AML;
3. 2nd or subsequent relapsed AML, but not previously treated according to protocol Relapsed AML 2001/01;
4. <18 years of age at initial diagnosis;
5. Signed informed consent.
|- Exclusion criteria||1. Symptomatic cardiac dysfunction (CTC grade 3 or 4), and/or a fractional shortening at echocardiography below 29%;
2. Karnofsky performance status <40% (children aged 16 years and older) or Lansky performance status of <40% (yougner children);
3. Any other organ dysfunction (CTC grade 4) that will interfere with the protocol treatment;
4. Inability to apply to the protocol for other reasons;
5. AML FAB type M3, acute promyelocytic leukemia, and/or t(15;17) and/or PML-RARalfa fusion gene.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||11-jan-2001|
|- planned closingdate||11-jan-2007|
|- Target number of participants||400|
|- Interventions||Addition of liposomal daunorubicin (DaunoXomeŽ) to FLAG in reinduction course I.|
|- Primary outcome||Percentage of BM blasts >20% after course I, determined 4-6 weeks after the start.|
|- Secondary outcome||1. Toxicity, focussing on but not limited to bone marrow aplasia, mucosal toxicity and cardiotoxicity;
2. Efficacy as determined by day 14 BM blasts, time to PB clearance of blasts, CR rate after 2 course of chemotherapy, % of patients that underwent SCT, overall survival, event-free survival and disease-free survival;
3. Clinical and cell biological features, and overall outcome of the entire cohort of patients with relapsed AML that has been registered in the time period of patient accrual (also including patients that were not treated according to this protocol).
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Dr. Gertjan J.L. Kaspers|
|- CONTACT for SCIENTIFIC QUERIES||Dr. Gertjan J.L. Kaspers|
|- Sponsor/Initiator ||Dutch Childhood Oncology Group (DCOG)|
(Source(s) of Monetary or Material Support)
|- Brief summary||Relapsed and refractory acute myeloid leukemia (AML) in children is a rare problem, but has a poor prognosis. |
We therefore designed an international multicenter open label randomised phase III trial in children with such a disease.
Reinduction treatment will be done with 2 courses of combination chemotherapy, with FLAG (fludarabine, ara-C and G-CSF) in both courses as standard treatment. In the first course there will be a randomisation for liposomal daunorubicin (DaunoXomeŽ) to be added or not. The second course should always concern FLAG.
If patients have >20% of blasts in the bone marrow after the 1st course, or if they are not in complete remission (CR) after the 2nd course, they will go off protocol.
Patients in CR after reinduction treatment can immediately proceed to stem cell transplantation. Consolidation chemotherapy should be given if SCT is delayed. A 3rd course of intensive chemotherapy (VP16 and continuous infusion with cytarabine) is the general recommendation. In selected patients, a low intensity consolidation may be preferred, and such a schedule is described as well.
The type of SCT is based on the risk-group. Preferably, a matched sibling donor (MSD) SCT is performed. If a MSD is not available all patients are candidates for a matched unrelated donor (MUD) SCT. If a MUD is also not available, patients with primary refractory disease, early relapse (within 1 year from diagnosis), or 2nd or higher relapse, are candidates for the more experimental haplo-identical donor (HID) SCT in view of the dismal prognosis. However, patients with a late relapse (>1 year from initial diagnosis) have a better prognosis and should be offered an autologous SCT if a MSD or MUD SCT is not possible. Only in case of autologous SCT, maintenance treatment and/or adjuvant immunotherapy could be considered.
Main objectives of the study:
are to determine the efficacy and toxicity of DaunoXomeŽ when added to FLAG in children with relapsed and refractory AML. In addition, the study will prospectively determine the clinical outcome of these patients, stratified according to the different risk groups (refractory disease, early relapse, late relapse, multiple relapse).
are to determine the clinical relevance of minimal residual measurements, in vitro cellular drug resistance data, cell biological and molecular features and pharmacokinetic data of DaunoXomeŽ, in these patients.
The study expects to accrue up to 100 patients annually, and will run about 4 years, to enroll a total of 360 randomised patients.
|- Main changes (audit trail)|
|- RECORD||16-aug-2005 - 10-nov-2010|