Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.

In a protocol of treatment of AML used in 1994 for adults with AML up to the age of 50 years, the Spanish CETLAM group showed a complete remission rate 75 % using the combination of daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous infusion during 7 days) and etoposide (100mg/m2 IV/day 3 days). If idarubicin (10 mg/m2, 3 days) was administered instead of daunorubicin, the complete remission (CR) rate in adults up to 60 years was 75%. To improve the proportion of CRs and to decrease relapse rate appearing in 50% of patients, the phase II AML-99 trial includes intermediate dose-cytarabine during induction and risk-adapted post remission treatment based on the improvement in prognostic characterization of AML and the implementation of novel transplantation techniques.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myelocytic, Acute
• Intervention / Treatment: Drug: Ara-C; Other: Autologous transplantation; Other: Allogeneic HLA-identical sibling transplantation; Other: CD34+ selection

Detailed Description

Induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.

Consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 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)] are treated with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5).
• Patients in intermediate cytogenetics group (normal karyotype and a single course to achieve the CR) receive an autologous peripheral blood stem cell (PBSC) transplant, regardless of having an HLA-identical sibling.
• The remaining patients are considered in the high-risk group and are treated with autologous or allogeneic PBSC transplantation depending on the availability of a sibling donor. In allotransplants, CD34+ cell selection of hematopoietic cells is performed.

• Study Type: Interventional
• Enrollment (Actual): 354
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08022
    • Centro Médico Teknon
  • Barcelona, Spain, 08036
    • Jordi Esteve
  • Girona, Spain, 17007
    • Hopital Universitari de Girona Dr. Josep Trueta
  • Lleida, Spain, 25006
    • Hospital Universitari Arnau de Vilanova
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Murcia, Spain, 30008
    • Hospital General Universitario de Murcia
  • Tarragona, Spain, 43007
    • Hospital Universitari Joan Xxiii
  • Terrassa, Spain, 08225
    • Mutua de Terrassa
  • Valencia, Spain, 496010
    • Hospital Clinico Universitario de Valencia
  • Valladolid, Spain, 41010
    • Hospital Universitario Rio Hortega
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
    • L'Hospitalet del Llobregat, Barcelona, Spain, 08907
      • ICO Hospital Universitari de Bellvitge
  • Coruña
    • A Coruña, Coruña, Spain, 15006
      • Hospital A Coruña
  • Mallorca
    • Palma de Mallorca, Mallorca, Spain, 07198
      • Hospital Universitari Son Espases
    • Palma de Mallorca, Mallorca, Spain, 07198
      • Joan Bargay
  • Tarragona
    • Tortosa, Tarragona, Spain, 43517
      • Hospital Verge de la Cinta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with newly diagnosed AML, classified by FAB criteria
• Age not superior to 60 years
• Verbal informed consent for the chemotherapy and written for the mobilization and stem cell transplantation

Exclusion Criteria:

• Patients treated previously for its AML with other chemotherapy different from hydroxyurea
• Acute promyelocytic leukemia (M3)
• Chronic myeloid leukemia in blastic crisis
• Leukemias appearing after other myeloproliferative processes
• Leukemias surviving after myelodysplastic syndromes with more than 6 months of evolution
• Presence of other neoplastic disease in activity
• Secondary AML which had appeared after cured malignancies (for instance Hodgkin disease) and those who are still exposed to alkylant agents or radiation
• Renal and hepatic abnormal function with creatinine values and/or bilirubin two times higher than the normal threshold, except when this alteration could be attributed to the leukemia
• Patients with a fraction of ejection very low (inferior to 40%), symptomatic cardiac insufficiency or both
• Patients with a grave concomitant neurological or psychiatric disease
• Positivity of HIV (donor and/or receptor)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Risk-adapted postremission treatment; Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection.

Drug: Ara-C; Intermediate dose during induction phase to remission.; High-dose during consolidation phase in patients with favorable cytogenetics.; Other: Autologous transplantation; In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission.; In patients with other cytogenetics without HLA-Identical sibling.; Other: Allogeneic HLA-identical sibling transplantation; Patients without favorable or normal karyotype(and one course to CR).; Patients with normal karyotype who need two cycles of chemotherapy to achieve CR, and other cytogenetics.; Other: CD34+ selection; In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate.	Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.	2 months.
Disease free survival.	Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.	4 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.	Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up.	4 years.
Feasibility to mobilize and collect autologous PBSC after consolidation phase.	Evaluation of mobilization failures.	6 months.
Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.	CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.	4 years.

Collaborators and Investigators

• Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Study record dates

Study Major Dates

• Study Start: September 1, 1998
• Primary Completion (Actual): September 1, 1998
• Study Completion (Actual): November 1, 2003

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: October 29, 2012
• First Posted (Estimate): October 30, 2012

Study Record Updates

• Last Update Posted (Estimate): November 1, 2012
• Last Update Submitted That Met QC Criteria: October 31, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Primary AML; Risk-adapted treatment; Hematopoietic transplantation; CD34+ cell selection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: AML-99