Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Phase 2

Completed

• Conditions: Leukemia, Myelocytic, Acute
• Interventions: Drug: Ara-C; Other: Autologous transplantation; Other: Allogeneic HLA-identical sibling transplantation; Other: CD34+ selection

• Registration Number: NCT01716793
• Lead Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

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.

Study Timeline

• Study Start: 1998-09
• Primary Completion: 1998-09
• Study Completion: 2003-11
• Status Verified: 2012-10
• Study First Submitted: 2012-10-22
• Study First Submitted QC: 2012-10-29
• Study First Posted: 2012-10-30
• Last Update Submitted: 2012-10-31
• Last Update Posted: 2012-11-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 354

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Risk-adapted postremission treatment	Allogeneic HLA-identical sibling transplantation	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.
Risk-adapted postremission treatment	CD34+ selection	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.
Risk-adapted postremission treatment	Autologous transplantation	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.
Risk-adapted postremission treatment	Ara-C	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.	4 years.	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.	6 months.	Evaluation of mobilization failures.
Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.	4 years.	CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up.

Trial Locations

Locations (19)

ICO Hospital Universitari de Bellvitge; 🇪🇸 L'Hospitalet del Llobregat, Barcelona, Spain

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Hospital A Coruña; 🇪🇸 A Coruña, Coruña, Spain

Hospital Verge de la Cinta; 🇪🇸 Tortosa, Tarragona, Spain

Hospital Universitari Son Espases; 🇪🇸 Palma de Mallorca, Mallorca, Spain

Centro Medico Teknon; 🇪🇸 Barcelona, Spain

Joan Bargay; 🇪🇸 Palma de Mallorca, Mallorca, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Jordi Esteve; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitari Arnau de Vilanova; 🇪🇸 Lleida, Spain

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hopital Universitari de Girona Dr. Josep Trueta; 🇪🇸 Girona, Spain

Hospital General Universitario de Murcia; 🇪🇸 Murcia, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Malaga, Spain

Mutua de Terrassa; 🇪🇸 Terrassa, Spain

Hospital Universitari Joan XXIII; 🇪🇸 Tarragona, Spain

Hospital Universitario Rio Hortega; 🇪🇸 Valladolid, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain