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

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.

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 Overview

• Status: Completed
• Conditions: Di Novo Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Idarubicin

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Badalona, Spain, 08916
    • Hospital Universitari Germans Trias I Pujol de Badalona
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial de Barcelona
  • Barcelona, Spain, 08035
    • HOSPITALS VALL D'HEBRON
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Idarubicin; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
• Collaborators: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau; Ministry of Health, Spain

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: October 1, 2012
• First Submitted That Met QC Criteria: October 2, 2012
• First Posted (ESTIMATE): October 4, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 28, 2016
• Last Update Submitted That Met QC Criteria: January 27, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: acute; Idarubicin; leukemia; myeloid; CETLAM
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Idarubicin
• Other Study ID Numbers: IIBSP-CSF-2011-141