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

• ClinicalTrials.gov Identifier: NCT01700413
• Recruitment Status: Completed
• First Posted: October 4, 2012
• Last Update Posted: January 28, 2016
• Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
• Collaborators: Ministry of Health, Spain; Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Information provided by (Responsible Party): Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Tracking Information

• First Submitted Date: October 1, 2012
• First Posted Date: October 4, 2012
• Last Update Posted Date: January 28, 2016
• Study Start Date: October 2012
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2012)

Rate of complete remissions (CR) [ Time Frame: From 28 up to 56 days after first induction ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 2, 2012)

• 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 ]
  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. ]
  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 ]
  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. ]
  Rate of patients that have relapsed within 6 months after complete remission.
• Survival at 9 months from diagnosis [ Time Frame: 9 months after diagnoses ]
  Rate of patients alive at 9 months after diagnosis.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Toxicity of Increasing Doses of Idarubicin, Cytarabine and G-CSF in Acute Myeloid Leukemia
• 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.

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Di Novo Acute Myeloid Leukemia
• Intervention: Drug: Idarubicin

Study Arms

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

Intervention: Drug: Idarubicin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 28, 2015): 48
• Original Estimated Enrollment (submitted: October 2, 2012): 45
• Actual Study Completion Date: April 2015
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT01700413
• Other Study ID Numbers: IIBSP-CSF-2011-141
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
• Study Sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

Collaborators

• Ministry of Health, Spain
• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Investigators

• Study Chair: Salut Brunet, MD; Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

• PRS Account: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
• Verification Date: January 2016