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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Sponsor:
Collaborators:
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Ministry of Health, Spain
Information provided by (Responsible Party):
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
ClinicalTrials.gov Identifier:
NCT01700413
First received: October 1, 2012
Last updated: February 12, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Di Novo Acute Myeloid Leukemia
Drug: Idarubicin
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 45
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)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700413

Contacts
Contact: Salut Brunet, MD + 34 93 434 44 12 investigacion@mfar.net
Contact: Federico Nepote, PhD + 34 93 434 44 12 federico.nepote@mfar.net

Locations
Spain
Hospital Universitari Germans Trias I Pujol de Badalona Recruiting
Badalona, Spain, 08916
Contact: Susana Vives, MD    +34934344412    investigacion@mfar.net   
Principal Investigator: Susana Vives, MD         
Hospital de La Santa Creu I Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Salut Brunet, MD    +34934344412    investigacion@mfar.net   
Principal Investigator: Salut Brunet, MD         
Hospital Clinic I Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Jordi Esteve, MD    +34934344412    investigacion@mfar.net   
Principal Investigator: Jordi Esteve, MD         
Hospitals Vall D'Hebron Not yet recruiting
Barcelona, Spain, 08035
Contact: Olga Salamero, MD    +34934344412    investigacion@mfar.net   
Principal Investigator: Olga Salamero, MD         
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Mar Tormo, MD    +34934344412    investigacion@mfar.net   
Principal Investigator: Mar Tormo, MD         
Sponsors and Collaborators
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Ministry of Health, Spain
Investigators
Study Chair: Salut Brunet, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  More Information

No publications provided

Responsible Party: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
ClinicalTrials.gov Identifier: NCT01700413     History of Changes
Other Study ID Numbers: IIBSP-CSF-2011-141
Study First Received: October 1, 2012
Last Updated: February 12, 2013
Health Authority: Spain: Spanish Agency of Medicines
Spain: Ethics Committee

Keywords provided by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias:
acute
myeloid
leukemia
CETLAM
Idarubicin

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 24, 2014