NCT00186966 · CITED IN SOURCE DOCUMENTS

Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2011-04-06

This is an international multicenter open label randomized phase III trial in children with relapsed and refractory acute myeloid leukemia (AML) such a disease. The main purpose of this study is to determine the efficacy and toxicity of liposomal daunorubicin when added to fludarabine, ara-C and G-CSF(FLAG) in children with relapsed and refractory AML.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: Inclusion Criteria: * Children and adolescents less than eighteen years of age at start of chemotherapy. * Subject has one of the following: Primary refractory AML, first relapsed AML, second or subsequent relapsed AML and was not previously treated according to this particular protocol * Subjects with a combined relapse, or an isolated extramedullary relapse, or a bone marrow relapse are eligible, also for randomization. Exclusion Criteria: * Symptomatic cardiac dysfunction. * Inadequate performance score. * Any other organ dysfunction that will interfere with the administration of the therapy. * FAB type M3
healthy Volunteers: false
maximum Age: 18 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome)
Drug: Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan
Procedure: Hematopoietic stem cell transplant
Radiation: Total body irradiation
label
FLAG
type
OTHER
intervention Names
Drug: Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome)
Drug: Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan
Procedure: Hematopoietic stem cell transplant
Radiation: Total body irradiation
label
FLAG and LP Dox
type
OTHER

interventions

arm Group Labels
FLAG
FLAG and LP Dox
description
See Detailed Description section for details of treatment interventions.
name
Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome)
type
DRUG
arm Group Labels
FLAG
FLAG and LP Dox
description
See Detailed Description section for details of treatment interventions.
name
Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan
type
DRUG
arm Group Labels
FLAG
FLAG and LP Dox
description
See Detailed Description section for details of treatment interventions.
name
Hematopoietic stem cell transplant
type
PROCEDURE
arm Group Labels
FLAG
FLAG and LP Dox
description
See Detailed Description section for details of treatment interventions.
name
Total body irradiation
type
RADIATION

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 394
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

measure
Response Rate
time Frame
8-9 years

secondary Outcomes

measure
Toxicity between two arms
time Frame
8-9 years

Full study description

brief Summary: This is an international multicenter open label randomized phase III trial in children with relapsed and refractory acute myeloid leukemia (AML) such a disease. The main purpose of this study is to determine the efficacy and toxicity of liposomal daunorubicin when added to fludarabine, ara-C and G-CSF(FLAG) in children with relapsed and refractory AML.
detailed Description: Secondary objectives of this trial are: * To determine the toxicity of liposomal daunorubicin when added to FLAG, in terms of mucosal toxicity, bone marrow aplasia, short- and long-term cardiotoxicity and other side effects as compared to patients treated with FLAG only. * To determine the long-term clinical outcome prospectively in a large group of children with refractory and relapsed acute myeloid leukemia. * To determine the changes in minimal residual disease over time, and the prognostic significance of minimal residual disease determined at various time-points. * To determine the relation between in vitro cellular drug resistance and clinical and cell biological features, minimal residual disease and clinical outcome in this patient group * To determine the pharmacokinetics of liposomal daunorubicin in relation to its toxicity and efficacy 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 (DaunoXome®) 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 greater than or equal to 2nd 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.

Source references

references

citation
Kaspers J, Zimmermann M, Fleischhack G, Tamminga R, Gibson B, Armendariz H, Dworzak M, Ha S, Hovi L, Maschan A, Philippe N, Razzouk B, Rizzari C, Smisek P, Smith O, Stark B, Will A, Creutzig U. Relapsed Acute Myeloid Leukemia in Children and Adolescents: Interim Report of the International Randomised Phase III Study Relapsed AML 2001/01. 2006 ASH Annual Meeting Abstracts 108: 2013.
type
RESULT