Efficacy and Toxicity of Increasing Doses of Idarubicin, Cytarabine and G-CSF in Acute Myeloid Leukemia

Study Overview
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Brief Summary
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While several studies have been reported with increasing doses of daunorubicin in the first line treatment of Acute Myeloid Leukemia (AML), there is no similar experience with idarubicin as initial treatment of AML. As idarubicin is the most common treatment used for AML, it is needed to find the optimal dose for the combination of idarubicin, cytarabine and G_CSF, to explore if this combination improves the outcomes of current treatments for AML. The aim of this dose-finding study is to find the optimal dose for the combination of idarubicin, cytarabine and G-CSF that could improve the response rate, reduce relapse and improve survival of patients with primary acute myeloid leukemia. This could be a significant advance in a field where treatment outcomes have stabilized in the last 15 years. This study will be the basis for further prospective, randomized, multicenter trial comparing idarubicin maximum tolerated dose, compared to standard treatment with idarubicin and cytarabine, including raising both arms in G-CSF. The dose of 12 mg/m2 will be administered as control arm in this future randomized study, which will investigate the benefit of enhanced dose identified as optimal in this phase II pilot study.

Official Title
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Treatment of di Novo Acute Myeloid Leukemia With the Combination of Increasing Doses of Idarubicin, Cytarabine and Sensitization (Priming) With G-CSF. A Phase II Prospective Study of Toxicity and Efficacy.

Conditions
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Di Novo Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Idarubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent signature Patients with newly diagnosed AML, classified according to WHO criteria. Age more than or equal to 18 and less than or equal to 70 years. Exclusion Criteria: Patients previously treated with chemotherapy for their AML other than hydroxyurea. Acute promyelocytic leukemia with t (15; 17). Blast crisis of chronic myeloid leukemia. Leukemias that appear after other myeloproliferative neoplasms. Leukemias ensuing myelodysplastic syndromes after more than 6 months. Presence of other malignancies in activity. AML secondary to chemo-radiotherapy treatment for other malignancies. Abnormal renal and hepatic function, with creatinine value and / or bilirubin 2 times the normal limit value, except where the alterations are attributable to leukemia. Patients with markedly reduced ejection fraction (less than 45%), symptomatic heart failure, or both of the normal value of the center. Patients with serious concomitant psychiatric or neurological disease. HIV-positive. Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idarubicin<br>Cohort 1: Idarubicin 14 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 2: Idarubicin 16 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day Cohort 3: Idarubicin 18 mg/m2 (day 1-3), Cytarabine 200 mg/m2 (Days 1-7), G-CSF 150 mcg/m2/day | Drug: Idarubicin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of complete remissions (CR) | Identify the highest dose of idarubicin in combination with cytarabine and G-CSF that produces a CR rate equal to or greater than 65% with tolerable toxicity. | From 28 up to 56 days after first induction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of patients with adverse events as a measure of safety and tolerability | Hematologic toxicity Gastrointestinal and liver toxicity Cardiac Toxicity Fever and infection Pulmonary complications Duration of hospitalization Mortality and causes of death induction. | Weekly during treatment, and on months 3 and 6 after complete response | 
| Duration of hospitalization | Number of days in which the patient is hospitalized. | From the inclusion until 9 months after inclusion. | 
| Mortality (as rate) related to study treatment | Causes of death, mortality related treatment, mortality in induction. | Weekly during treatment, 3 months after complete remission, 6 months after complete remission and 9 months after complete remission | 
| Relapse at 6 months | Rate of patients that have relapsed within 6 months after complete remission. | 6 months from complete remission, expected to be within 9 months from inclusion. | 
| Survival at 9 months from diagnosis | Rate of patients alive at 9 months after diagnosis. | 9 months after diagnoses | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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acute, myeloid, leukemia, CETLAM, Idarubicin