Acute Myeloid LeukemiaPhase 3NCT00186966
Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
A Phase 3 study testing Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome), Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan and Hematopoietic stem cell transplant in people with Acute Myeloid Leukemia, run by Dutch Childhood Oncology Group at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome), Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan and Hematopoietic stem cell transplant
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 394 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2002to Sep 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- Symptomatic cardiac dysfunction.
- Inadequate performance score.
- Any other organ dysfunction that will interfere with the administration of the therapy.
- FAB type M3
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: A Randomized Phase III Study of the Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome), Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan, Hematopoietic stem cell transplant, Total body irradiation
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome)Drug
See Detailed Description section for details of treatment interventions.
Etoposide, Thioguanine, Cyclophosphamide, Busulfan, MelphalanDrug
See Detailed Description section for details of treatment interventions.
Hematopoietic stem cell transplantProcedure or surgery
See Detailed Description section for details of treatment interventions.
Total body irradiationRadiation
See Detailed Description section for details of treatment interventions.
| Study group | Role | What they receive |
|---|---|---|
| FLAG | Other | Not described Receives: Drug: Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome); Drug: Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan; Procedure: Hematopoietic stem cell transplant; Radiation: Total body irradiation |
| FLAG and LP Dox | Other | Not described Receives: Drug: Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome); Drug: Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan; Procedure: Hematopoietic stem cell transplant; Radiation: Total body irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Measured: 8-9 years
Secondary outcomes (1)
Toxicity between two arms
Measured: 8-9 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startMar 2002
- Primary completionApr 2009
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 394 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dutch Childhood Oncology Group
- Sponsor type
- University, hospital or other
- Collaborators
- International BFM Study Group, St. Jude Children's Research Hospital
- Investigators
- Jeffrey Rubnitz, M.D., Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00186966
- Sponsor's protocol ID
- TRIAL
- Other IDs
- TRIAL Relapsed AML 2001/01
- Status last verified
- Apr 2011
- First submitted
- 12 Sep 2005
- Last updated
- 6 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase III Study of the Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00186966
- Acronym / sponsor ID
- TRIAL
- Conditions
- Acute Myeloid Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 394 participants (actual)
- Lead sponsor
- Dutch Childhood Oncology GroupUniversity, hospital or other
- Collaborators
- International BFM Study Group, St. Jude Children's Research Hospital
- Study start
- Mar 2002
- Primary completion
- Apr 2009 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FLAG | Other | Drug: Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome), Drug: Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan, Procedure: Hematopoietic stem cell transplant, Radiation: Total body irradiation |
| FLAG and LP Dox | Other | Drug: Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome), Drug: Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan, Procedure: Hematopoietic stem cell transplant, Radiation: Total body irradiation |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (4 listed)
- Symptomatic cardiac dysfunction.
- Inadequate performance score.
- Any other organ dysfunction that will interfere with the administration of the therapy.
- FAB type M3
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome)See Detailed Description section for details of treatment interventions. | Drug | FLAG, FLAG and LP Dox |
| Etoposide, Thioguanine, Cyclophosphamide, Busulfan, MelphalanSee Detailed Description section for details of treatment interventions. | Drug | FLAG, FLAG and LP Dox |
| Hematopoietic stem cell transplantSee Detailed Description section for details of treatment interventions. | Procedure or surgery | FLAG, FLAG and LP Dox |
| Total body irradiationSee Detailed Description section for details of treatment interventions. | Radiation | FLAG, FLAG and LP Dox |
Primary outcome
Response Rate
Time frame: 8-9 years
1 secondary outcome
Toxicity between two arms
Time frame: 8-9 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2011.
- Results publicationKaspers 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.
- St. Jude Children's Research HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Rubnitz, M.D. principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fludarabine, Cytarabine, Liposomal daunorubicin (DaunoXome), Etoposide, Thioguanine, Cyclophosphamide, Busulfan, Melphalan and Hematopoietic stem cell transplant in people with Acute Myeloid Leukemia, run by Dutch Childhood Oncology Group at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (time frame: 8-9 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00186966, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2011.