Efficacy and Toxicity of Increasing Doses of Idarubicin, Cytarabine and G-CSF in Acute Myeloid Leukemia
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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.|
- Rate of complete remissions (CR) [ Time Frame: From 28 up to 56 days after first induction ] [ Designated as safety issue: No ]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.
- Rate of patients with adverse events as a measure of safety and tolerability [ Time Frame: Weekly during treatment, and on months 3 and 6 after complete response ] [ Designated as safety issue: Yes ]Hematologic toxicity Gastrointestinal and liver toxicity Cardiac Toxicity Fever and infection Pulmonary complications Duration of hospitalization Mortality and causes of death induction.
- Duration of hospitalization [ Time Frame: From the inclusion until 9 months after inclusion. ] [ Designated as safety issue: No ]Number of days in which the patient is hospitalized.
- Mortality (as rate) related to study treatment [ Time Frame: Weekly during treatment, 3 months after complete remission, 6 months after complete remission and 9 months after complete remission ] [ Designated as safety issue: Yes ]Causes of death, mortality related treatment, mortality in induction.
- Relapse at 6 months [ Time Frame: 6 months from complete remission, expected to be within 9 months from inclusion. ] [ Designated as safety issue: No ]Rate of patients that have relapsed within 6 months after complete remission.
- Survival at 9 months from diagnosis [ Time Frame: 9 months after diagnoses ] [ Designated as safety issue: No ]Rate of patients alive at 9 months after diagnosis.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
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
|Contact: Salut Brunet, MD||+ 34 93 434 44 firstname.lastname@example.org|
|Contact: Federico Nepote, PhD||+ 34 93 434 44 email@example.com|
|Hospital Universitari Germans Trias I Pujol de Badalona||Recruiting|
|Badalona, Spain, 08916|
|Contact: Susana Vives, MD +34934344412 firstname.lastname@example.org|
|Principal Investigator: Susana Vives, MD|
|Hospital de La Santa Creu I Sant Pau||Recruiting|
|Barcelona, Spain, 08025|
|Contact: Salut Brunet, MD +34934344412 email@example.com|
|Principal Investigator: Salut Brunet, MD|
|Hospital Clinic I Provincial de Barcelona||Recruiting|
|Barcelona, Spain, 08036|
|Contact: Jordi Esteve, MD +34934344412 firstname.lastname@example.org|
|Principal Investigator: Jordi Esteve, MD|
|Hospitals Vall D'Hebron||Not yet recruiting|
|Barcelona, Spain, 08035|
|Contact: Olga Salamero, MD +34934344412 email@example.com|
|Principal Investigator: Olga Salamero, MD|
|Hospital Clínico Universitario de Valencia||Recruiting|
|Valencia, Spain, 46010|
|Contact: Mar Tormo, MD +34934344412 firstname.lastname@example.org|
|Principal Investigator: Mar Tormo, MD|
|Study Chair:||Salut Brunet, MD||Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau|