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Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
ClinicalTrials.gov Identifier:
NCT01716793
First received: October 22, 2012
Last updated: October 31, 2012
Last verified: October 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Leukemia, Myelocytic, Acute
 Drug: Ara-C
Other: Autologous transplantation
Other: Allogeneic HLA-identical sibling transplantation
Other: CD34+ selection
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.

Resource links provided by NLM:

Drug Information available for: Cytarabine
U.S. FDA Resources

Further study details as provided by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias:

Primary Outcome Measures:
  • Complete remission rate. [ Time Frame: 2 months. ] [ Designated as safety issue: Yes ]
    Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.

  • Disease free survival. [ Time Frame: 4 years. ] [ Designated as safety issue: No ]
    Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.


Secondary Outcome Measures:
  • Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment. [ Time Frame: 4 years. ] [ Designated as safety issue: No ]
    Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up.

  • Feasibility to mobilize and collect autologous PBSC after consolidation phase. [ Time Frame: 6 months. ] [ Designated as safety issue: No ]
    Evaluation of mobilization failures.

  • Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome. [ Time Frame: 4 years. ] [ Designated as safety issue: Yes ]
    CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.


Enrollment: 354
Study Start Date: September 1998
Study Completion Date: November 2003
Primary Completion Date: September 1998 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01716793

Locations
Spain
Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
ICO Hospital Universitari de Bellvitge
L'Hospitalet del Llobregat, Barcelona, Spain, 08907
Hospital A Coruña
A Coruña, Coruña, Spain, 15006
Hospital Universitari Son Espases
Palma de Mallorca, Mallorca, Spain, 07198
Joan Bargay
Palma de Mallorca, Mallorca, Spain, 07198
Hospital Verge de la Cinta
Tortosa, Tarragona, Spain, 43517
Centro Medico Teknon
Barcelona, Spain, 08022
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital del Mar
Barcelona, Spain, 08003
Jordi Esteve
Barcelona, Spain, 08036
Hopital Universitari de Girona Dr. Josep Trueta
Girona, Spain, 17007
Hospital Universitari Arnau de Vilanova
Lleida, Spain, 25006
Hospital Universitario Virgen de la Victoria
Malaga, Spain, 29010
Hospital General Universitario de Murcia
Murcia, Spain, 30008
Hospital Universitari Joan XXIII
Tarragona, Spain, 43007
Mutua de Terrassa
Terrassa, Spain, 08225
Hospital Clínico Universitario de Valencia
Valencia, Spain, 496010
Hospital Universitario Rio Hortega
Valladolid, Spain, 41010
Sponsors and Collaborators
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Investigators
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
  More Information

No publications provided

Responsible Party: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
ClinicalTrials.gov Identifier: NCT01716793     History of Changes
Other Study ID Numbers: AML-99
Study First Received: October 22, 2012
Last Updated: October 31, 2012
Health Authority: Spain: Comité Ético de Investigación Clínica

Keywords provided by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias:
Primary AML
Risk-adapted treatment
Hematopoietic transplantation
CD34+ cell selection

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 19, 2013