Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Status and phase: Completed; Phase 2

Conditions: Leukemia, Myelocytic, Acute

Treatments: Other: CD34+ selection; Other: Autologous transplantation; Other: Allogeneic HLA-identical sibling transplantation; Drug: Ara-C

Study type: Interventional

Funder types: Other

Identifiers

NCT01716793

AML-99

Details and patient eligibility

About

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.

Full 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.

Enrollment: 354 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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354 participants in 1 patient group

Risk-adapted postremission treatment

Other group

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.

Treatment:

Other: Autologous transplantation

Drug: Ara-C

Other: CD34+ selection

Other: Allogeneic HLA-identical sibling transplantation