Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Leukemia, Myelocytic, Acute Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01716793
• Other study ID #: AML-99
• Status: Completed
• Phase: Phase 2
• First received: October 22, 2012
• Last updated: October 31, 2012
• Start date: September 1998
• Est. completion date: November 2003

Study information

• Verified date: October 2012
• Source: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 354
• Est. completion date: November 2003
• Est. primary completion date: September 1998
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Myelocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.
• 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.
• CD34+ selection
In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.

Locations

Country	Name	City	State
Spain	Hospital A Coruña	A Coruña	Coruña
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Centro Medico Teknon	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Jordi Esteve	Barcelona
Spain	Hopital Universitari de Girona Dr. Josep Trueta	Girona
Spain	ICO Hospital Universitari de Bellvitge	L'Hospitalet del Llobregat	Barcelona
Spain	Hospital Universitari Arnau de Vilanova	Lleida
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital General Universitario de Murcia	Murcia
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Mallorca
Spain	Joan Bargay	Palma de Mallorca	Mallorca
Spain	Hospital Universitari Joan XXIII	Tarragona
Spain	Mutua de Terrassa	Terrassa
Spain	Hospital Verge de la Cinta	Tortosa	Tarragona
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Rio Hortega	Valladolid

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate.	Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission.	2 months.	Yes
Primary	Disease free survival.	Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.	4 years.	No
Secondary	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.	No
Secondary	Feasibility to mobilize and collect autologous PBSC after consolidation phase.	Evaluation of mobilization failures.	6 months.	No
Secondary	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.	Yes