NCT01723657

Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)

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.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 862 (actual)
• Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
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	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.

Timeline

• Start date: 2003-10-01
• Primary completion: 2012-03-01
• Completion: 2012-03-01
• First posted: 2012-11-08
• Last updated: 2012-11-08

Locations

21 sites across 1 country: Spain