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Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT01723657
Recruitment Status : Completed
First Posted : November 8, 2012
Last Update Posted : November 8, 2012
Sponsor:
Information provided by (Responsible Party):
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Brief 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 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.


Condition or disease Intervention/treatment Phase
Leukemia, Myelocytic, Acute 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 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 862 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Study Start Date : October 2003
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012


Arm Intervention/treatment
Risk-adapted postremission treatment.
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.
Drug: Ara-C
  • Intermediate dose during induction phase to remission.
  • High dose during consolidation phase in patients with favorable cytogenetics and leukocyte index below 20.

Other: 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: Allogeneic matched related or unrelated donor transplant.
-Patients without favorable/intermediate characteristics.

Drug: G-CSF
  • 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.
Other Name: Filgastrim.

Other: CD34+ selection.
-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.

Other: Mylotarg purging before autologous PBSC transplantation
Patients without favorable/intermediate characteristics and without matched related donor.




Primary Outcome Measures :
  1. 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.

  2. 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.



Secondary Outcome Measures :
  1. Toxicity in patients over 60 years old. [ Time Frame: 4 years. ]
    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.

  2. Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment. [ Time Frame: 4 years. ]
    Study the immunophenotype characteristics and/or molecular markers at diagnosis, and during the different treatment phases.

  3. Feasibility of post-remission treatment in patients with 60 or more years old. [ Time Frame: 4 years. ]
    Study the effect of post-remission treatments in patients with more than 60 years to evaluate the success of consolidation treatments.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with newly diagnosed AML, classified using OMS criteria.
  • Patients with 70 years old or younger.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01723657


Locations
Show Show 21 study locations
Sponsors and Collaborators
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Investigators
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Principal Investigator: Jorge Sierra, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Study Chair: Salut Brunet, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
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Responsible Party: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
ClinicalTrials.gov Identifier: NCT01723657    
Other Study ID Numbers: AML-03
First Posted: November 8, 2012    Key Record Dates
Last Update Posted: November 8, 2012
Last Verified: October 2012
Keywords provided by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias:
Leukemia
Myeloid
Acute
Young
CETLAM
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Gemtuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents