Leukemia, Myelocytic, AcutePhase 2NCT01723657
Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)
A Phase 2 study testing Ara-C, Autologous peripheral blood stem cell transplantation. and Allogeneic matched related or unrelated donor transplant. in people with Leukemia, Myelocytic, Acute, run by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias at 21 sites in Spain.
Trial summary
The AML-03 regimen investigates the addition of G-CSF priming to both induction and consolidation chemotherapies administrated in the previous AML-99 trial (NCT01716793) refines risk-stratification based on biological characterization also the AML-03 trial incorporates novel approaches for hematopoietic stem cell… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Myelocytic, Acute
- What is being tested?
- Ara-C, Autologous peripheral blood stem cell transplantation. and Allogeneic matched related or unrelated donor transplant.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 862 participants
- Where
- 21 sitesSpain
- Study dates
- Oct 2003to Mar 2012
- Phase
- Phase 2
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with newly diagnosed AML, classified using OMS criteria.
- Patients with 70 years old or younger.
Who cannot join
- Patients previously treated for the AML with chemotherapy different from hidroxiurea.
- Acute promyelocytic leukemia with t(15;17).
- Cronic mieloid leukemia in blastic crisis.
- Leukemias that appear after other myeloproliferative processes.
- Leukemias that survive after myelodysplasic syndromes of more than 6 months of evolution.
- Presence of other neoplasic disease in activity.
Show all 11Show fewer
- Secondary AML which appears after cured malignant disease (for instance, Hodgking disease), and those who are still exposed to alkilant agents or radiation.
- Abnormal renal and hepatic functions with creatinin and/or bilirrubine 2 times higher than the normal threshold, except when the alteration should be attributed to the leukemia.
- Patient with an ejection fraction below 40%, symptomatic cardiac deficiency or both.
- Patients with neurological or concomitant psychiatric disease.
- Positivity by HIV.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Spain21 sites
Hospital A Coruña
A Coruña, Coruña, 15006
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital del Mar
Barcelona, Barcelona, 08003
Centro Medico Teknon
Barcelona, Barcelona, 08022
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Hospital Vall d'Hebron
Barcelona, Barcelona, 08035
Hospital Clínic de Barcelona
Barcelona, Barcelona, 08036
Hopital Universitari de Girona Dr. Josep Trueta
Girona, Girona, 17007
ICO Hospital Universitari de Bellvitge
L'Hospitalet Del Llobregat, Barcelona, 08907
Hospital Universitari Arnau de Vilanova
Lleida, Lleida, 25006
Hospital Universitario La Paz
Madrid, Madrid, 28046
Hospital Universitario Virgen de la Victoria
Málaga, Malaga, 29010
Hospital General Universitario de Murcia
Murcia, Murcia, 30008
Hospital Universitari Son Espases
Palma de Mallorca, Mallorca, 07198
Hospital Universitari Son Dureta
Palma de Mallorca, Mallorca
Hospital Universitario Virgen del Rocio
Seville, Sevilla, 41014
Hospital Universitari Joan XXIII
Tarragona, Tarragona, 43007
Mutua de Terrassa
Terrassa, Terrassa, 08225
Hospital Verge de la Cinta
Tortosa, Tarragona, 43517
Hospital Clinico Universitario de Valencia
Valencia, Valencia, 46010
Hospital Universitario Rio Hortega
Valladolid, Valladolid, 41010
About this study
Official title: Risk Adapted Treatment for Primary AML in Adults, Based on Genetics and Minimal Residual Disease (MRD) in Patients up to the Age of 70 Years.
The AML-03 regimen investigates the addition of G-CSF priming to both induction and consolidation chemotherapies administrated in the previous AML-99 trial (NCT01716793) refines risk-stratification based on biological characterization also the AML-03 trial incorporates novel approaches for hematopoietic stem cell transplantation: such as Mylotarg™ "in vivo purging" in autografts, extends unrelated volunteers donors for allotransplants in high-risk patients, and introduces reduced intensity conditioning in patients with elder age (more than 50 years old).
The aims of these modifications are to analyse eficacy and toxicity of this induction and consolidation therapy and to analyse the disease free survival in patients who achieved complete response following a risk adjusted therapy.
Read the detailed description
Induction chemotherapy: idarubicin (12mg/m2/day intravenous, days 1, 3 and 5), intermediate-dose cytarabine (500mg/m2/12h, intravenous, days 1, 3 and 5) and etoposide (100mg/m2/day, intravenous, from day 1 to 3) as in AML-99 trial (NCT01716793), with the addition of subcutaneous G-CSF from day 0 to the last day of chemotherapy. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.
Consolidation therapy (as in AML-99 trial): mitoxantrone (12mg/m2/day, intravenous, days 4 to 6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).
Risk-stratification according to cytogenetics, courses to CR and availability of an HLA-identical sibling:
- Patients in the favorable cytogenetics group [t(8;21), inv(16) or t(16;16)] and Leukocyte index <20 at diagnosis (LI=white blood cell count (WBC) x (blasts in bone marrow/100) are treated with one course of high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5), but in case of LI>20 at diagnosis the intention is to perform an autologous peripheral blood stem cell (PBSC) transplantation.
- Patients in intermediate risk group, with normal karyotype, a single course of induction chemotherapy to achieve the CR, the absence of adverse molecular features (FLT3-ITD or MLL-PTD) and low minimal residual disease levels after consolidation (MRD<0,1%) receive an autologous PBSC transplant, regardless of having an HLA-identical sibling.
- The remaining patients defined as high-risk patients are treated with an allogeneic stem cell transplantation. Depending on the age, if the patient has an HLA-identical sibling donor, up to age of 50 years old it is performed with conventional conditioning therapy and positive selection of CD34+, older patients receive a reduced intensity conditioning regimen.
- Very high risk patients without a sibling are allocated to unrelated donor (9-10/10). Patients with adverse cytogenetics and/or FLT3-ITD without an adequate donor received Mylotarg™ as "in vivo purging" followed by an autologous PBSC transplantation.
- Conditions
- Leukemia, Myelocytic, Acute
- Being tested
- Ara-C, Autologous peripheral blood stem cell transplantation., Allogeneic matched related or unrelated donor transplant., G-CSF, CD34+ selection.
- Keywords
- Leukemia, Myeloid, Acute, Young, CETLAM
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ara-CDrug
- Intermediate dose during induction phase to remission.
- High dose during consolidation phase in patients with favorable cytogenetics and leukocyte index below 20.
Autologous peripheral blood stem cell transplantation.Other
- In patients with favorable cytogenetics with a Leukocyte index above 20.
- Patients with normal karyotype, and one cycle of chemotherapy to achieve complete remission, without adverse molecular and/or minimal residual disease (MRD) characteristics, regardless availability of a matched donor.
Allogeneic matched related or unrelated donor transplant.Other
-Patients without favorable/intermediate characteristics.
G-CSFDrug
Also called Filgastrim.
- Administration at induction phase to remission, days 0 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatmen arises 30x10e9/L.
- Administration at consolidation phase, days 4 to 6 (3 doses). G-CSF will be interrupted if the leukocyte count during treatment arises 30x10e9/L.
CD34+ selection.Other
-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.
Mylotarg purging before autologous PBSC transplantationOther
Patients without favorable/intermediate characteristics and without matched related donor.
| Study group | Role | What they receive |
|---|---|---|
| Risk-adapted postremission treatment. | Other | Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation. Receives: Drug: Ara-C; Other: Autologous peripheral blood stem cell transplantation.; Other: Allogeneic matched related or unrelated donor transplant.; Drug: G-CSF; Other: CD34+ selection.; Other: Mylotarg purging before autologous PBSC transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission rate (CRR)
Analyze the efficacy and toxicity of IDICE-G (idarubicin, intermediate doses of ara-C and etoposide) and G-CSF to achieve complete remission.
Measured: 2 months.
Disease free survival (DFS).
Analyze the disease free suvival of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.
Mortality in remission after chemotherapy and/or peripheral blood stem cell tranplantation.
Measured: 4 years.
Secondary outcomes (3)
Toxicity in patients over 60 years old.
Toxicity of the induction and intensification treatment in patients with more than 60 years old, in terms of unexpected adverse drug reaction, morbidity and mortality.
Measured: 4 years.
Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment.
Study the immunophenotype characteristics and/or molecular markers at diagnosis, and during the different treatment phases.
Measured: 4 years.
Feasibility of post-remission treatment in patients with 60 or more years old.
Study the effect of post-remission treatments in patients with more than 60 years to evaluate the success of consolidation treatments.
Measured: 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2012 (estimated)
- Study startOct 2003
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myelocytic, AcuteStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 862 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jorge Sierra, MD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauSalut Brunet, MD, Study chair, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723657
- Sponsor's protocol ID
- AML-03
- Status last verified
- Oct 2012
- First submitted
- 31 Oct 2012
- Last updated
- 8 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk Adapted Treatment for Primary AML in Adults, Based on Genetics and Minimal Residual Disease (MRD) in Patients up to the Age of 70 Years.
- ClinicalTrials.gov ID
- NCT01723657
- Acronym / sponsor ID
- AML-03
- Conditions
- Leukemia, Myelocytic, Acute
- Keywords
- Leukemia, Myeloid, Acute, Young, CETLAM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 862 participants (actual)
- Lead sponsor
- Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y MielodisplasiasUniversity, hospital or other
- Study start
- Oct 2003
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 8 Nov 2012 (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.
The AML-03 regimen investigates the addition of G-CSF priming to both induction and consolidation chemotherapies administrated in the previous AML-99 trial (NCT01716793) refines risk-stratification based on biological characterization also the AML-03 trial incorporates novel approaches for hematopoietic stem cell transplantation: such as Mylotarg™ "in vivo purging" in autografts, extends unrelated volunteers donors for allotransplants in high-risk patients, and introduces reduced intensity conditioning in patients with elder age (more than 50 years old).
The aims of these modifications are to analyse eficacy and toxicity of this induction and consolidation therapy and to analyse the disease free survival in patients who achieved complete response following a risk adjusted therapy.
Detailed description
Induction chemotherapy: idarubicin (12mg/m2/day intravenous, days 1, 3 and 5), intermediate-dose cytarabine (500mg/m2/12h, intravenous, days 1, 3 and 5) and etoposide (100mg/m2/day, intravenous, from day 1 to 3) as in AML-99 trial (NCT01716793), with the addition of subcutaneous G-CSF from day 0 to the last day of chemotherapy. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.
Consolidation therapy (as in AML-99 trial): mitoxantrone (12mg/m2/day, intravenous, days 4 to 6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).
Risk-stratification according to cytogenetics, courses to CR and availability of an HLA-identical sibling:
- Patients in the favorable cytogenetics group [t(8;21), inv(16) or t(16;16)] and Leukocyte index <20 at diagnosis (LI=white blood cell count (WBC) x (blasts in bone marrow/100) are treated with one course of high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5), but in case of LI>20 at diagnosis the intention is to perform an autologous peripheral blood stem cell (PBSC) transplantation.
- Patients in intermediate risk group, with normal karyotype, a single course of induction chemotherapy to achieve the CR, the absence of adverse molecular features (FLT3-ITD or MLL-PTD) and low minimal residual disease levels after consolidation (MRD<0,1%) receive an autologous PBSC transplant, regardless of having an HLA-identical sibling.
- The remaining patients defined as high-risk patients are treated with an allogeneic stem cell transplantation. Depending on the age, if the patient has an HLA-identical sibling donor, up to age of 50 years old it is performed with conventional conditioning therapy and positive selection of CD34+, older patients receive a reduced intensity conditioning regimen.
- Very high risk patients without a sibling are allocated to unrelated donor (9-10/10). Patients with adverse cytogenetics and/or FLT3-ITD without an adequate donor received Mylotarg™ as "in vivo purging" followed by an autologous PBSC transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Risk-adapted postremission treatment. | Other | Drug: Ara-C, Other: Autologous peripheral blood stem cell transplantation., Other: Allogeneic matched related or unrelated donor transplant., Drug: G-CSF, Other: CD34+ selection., Other: Mylotarg purging before autologous PBSC transplantationAra-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with newly diagnosed AML, classified using OMS criteria.
- Patients with 70 years old or younger.
Key exclusion criteria (11 listed)
- Patients previously treated for the AML with chemotherapy different from hidroxiurea.
- Acute promyelocytic leukemia with t(15;17).
- Cronic mieloid leukemia in blastic crisis.
- Leukemias that appear after other myeloproliferative processes.
- Leukemias that survive after myelodysplasic syndromes of more than 6 months of evolution.
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 |
|---|---|---|
| Ara-C* Intermediate dose during induction phase to remission. * High dose during consolidation phase in patients with favorable cytogenetics and leukocyte index below 20. | Drug | Risk-adapted postremission treatment. |
| Autologous peripheral blood stem cell transplantation.* In patients with favorable cytogenetics with a Leukocyte index above 20. * Patients with normal karyotype, and one cycle of chemotherapy to achieve complete remission, without adverse molecular and/or minimal residual disease (MRD) characteristics, regardless availability of a matched donor. | Other | Risk-adapted postremission treatment. |
| Allogeneic matched related or unrelated donor transplant.-Patients without favorable/intermediate characteristics. | Other | Risk-adapted postremission treatment. |
| G-CSFAlso: Filgastrim.* Administration at induction phase to remission, days 0 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatmen arises 30x10e9/L. * Administration at consolidation phase, days 4 to 6 (3 doses). G-CSF will be interrupted if the leukocyte count during treatment arises 30x10e9/L. | Drug | Risk-adapted postremission treatment. |
| CD34+ selection.-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed. | Other | Risk-adapted postremission treatment. |
| Mylotarg purging before autologous PBSC transplantationPatients without favorable/intermediate characteristics and without matched related donor. | Other | Risk-adapted postremission treatment. |
Primary outcome
Complete remission rate (CRR)
Time frame: 2 months.
Analyze the efficacy and toxicity of IDICE-G (idarubicin, intermediate doses of ara-C and etoposide) and G-CSF to achieve complete remission.
Disease free survival (DFS).
Time frame: 4 years.
Analyze the disease free suvival of patients in remission, with a therapeutic strategy adjusted to the prognostic factors. Mortality in remission after chemotherapy and/or peripheral blood stem cell tranplantation.
3 secondary outcomes
Toxicity in patients over 60 years old.
Time frame: 4 years.
Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment.
Time frame: 4 years.
Feasibility of post-remission treatment in patients with 60 or more years old.
Time frame: 4 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 8 Nov 2012.
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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.
Jorge Sierra, MD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Salut Brunet, MD study chair
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ara-C, Autologous peripheral blood stem cell transplantation. and Allogeneic matched related or unrelated donor transplant. in people with Leukemia, Myelocytic, Acute, run by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias at 21 sites in Spain.
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 2 inclusion and 11 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 8 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Complete remission rate (CRR) (time frame: 2 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Nov 2012.