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Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Primary Purpose

Leukemia, Myelocytic, Acute

Status
Completed
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Ara-C
Autologous transplantation
Allogeneic HLA-identical sibling transplantation
CD34+ selection
Sponsored by
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myelocytic, Acute focused on measuring Primary AML, Risk-adapted treatment, Hematopoietic transplantation, CD34+ cell selection

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Hospital Germans Trias i Pujol
  • ICO Hospital Universitari de Bellvitge
  • Hospital A Coruña
  • Hospital Universitari Son Espases
  • Joan Bargay
  • Hospital Verge de la Cinta
  • Hospital del Mar
  • Centro Medico Teknon
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Vall d'Hebron
  • Jordi Esteve
  • Hopital Universitari de Girona Dr. Josep Trueta
  • Hospital Universitari Arnau de Vilanova
  • Hospital Universitario Virgen de la Victoria
  • Hospital General Universitario de Murcia
  • Hospital Universitari Joan XXIII
  • Mutua de Terrassa
  • Hospital Clínico Universitario de Valencia
  • Hospital Universitario Rio Hortega

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Risk-adapted postremission treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Complete remission rate.
Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.
Disease free survival.
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.
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.
Evaluation of mobilization failures.
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.

Full Information

First Posted
October 22, 2012
Last Updated
October 31, 2012
Sponsor
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
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1. Study Identification

Unique Protocol Identification Number
NCT01716793
Brief Title
Risk-adapted Therapy for Adult Acute Myeloid Leukemia.
Official Title
Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
September 1998 (Actual)
Study Completion Date
November 2003 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelocytic, Acute
Keywords
Primary AML, Risk-adapted treatment, Hematopoietic transplantation, CD34+ cell selection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
354 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Risk-adapted postremission treatment
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ara-C
Intervention Description
Intermediate dose during induction phase to remission. High-dose during consolidation phase in patients with favorable cytogenetics.
Intervention Type
Other
Intervention Name(s)
Autologous transplantation
Intervention Description
In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission. In patients with other cytogenetics without HLA-Identical sibling.
Intervention Type
Other
Intervention Name(s)
Allogeneic HLA-identical sibling transplantation
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
CD34+ selection
Intervention Description
In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.
Primary Outcome Measure Information:
Title
Complete remission rate.
Description
Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.
Time Frame
2 months.
Title
Disease free survival.
Description
Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.
Time Frame
4 years.
Secondary Outcome Measure Information:
Title
Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.
Description
Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up.
Time Frame
4 years.
Title
Feasibility to mobilize and collect autologous PBSC after consolidation phase.
Description
Evaluation of mobilization failures.
Time Frame
6 months.
Title
Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.
Description
CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.
Time Frame
4 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Sierra, MD
Organizational Affiliation
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Salut Brunet, MD
Organizational Affiliation
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
ICO Hospital Universitari de Bellvitge
City
L'Hospitalet del Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital A Coruña
City
A Coruña
State/Province
Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitari Son Espases
City
Palma de Mallorca
State/Province
Mallorca
ZIP/Postal Code
07198
Country
Spain
Facility Name
Joan Bargay
City
Palma de Mallorca
State/Province
Mallorca
ZIP/Postal Code
07198
Country
Spain
Facility Name
Hospital Verge de la Cinta
City
Tortosa
State/Province
Tarragona
ZIP/Postal Code
43517
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Centro Medico Teknon
City
Barcelona
ZIP/Postal Code
08022
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Jordi Esteve
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hopital Universitari de Girona Dr. Josep Trueta
City
Girona
ZIP/Postal Code
17007
Country
Spain
Facility Name
Hospital Universitari Arnau de Vilanova
City
Lleida
ZIP/Postal Code
25006
Country
Spain
Facility Name
Hospital Universitario Virgen de la Victoria
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital General Universitario de Murcia
City
Murcia
ZIP/Postal Code
30008
Country
Spain
Facility Name
Hospital Universitari Joan XXIII
City
Tarragona
ZIP/Postal Code
43007
Country
Spain
Facility Name
Mutua de Terrassa
City
Terrassa
ZIP/Postal Code
08225
Country
Spain
Facility Name
Hospital Clínico Universitario de Valencia
City
Valencia
ZIP/Postal Code
496010
Country
Spain
Facility Name
Hospital Universitario Rio Hortega
City
Valladolid
ZIP/Postal Code
41010
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

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