IA14 Induction in Young Acute Myeloid Leukemia

Dose-intense Idarubicin Induction in Young Patients With Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous disease characterized by the clonal expansion of undifferentiated myeloid precursors. Although induction chemotherapy with cytarabine and daunorubicin/Idarubicin, typically called "7+3", has not changed for several decades, the best dosage of anthracycline is still unknown. Several prospective trials have demonstrated that intense dosage of anthracycline improved complete remission (CR) and overall survival (OS). Idarubicin 12mg/m2 (IA12) has been shown to be equal to dose intense daunorubicin (90 mg/m2 ) for achieving CR. Dose-intense daunorubicin 90 mg/m2 (DA90) has been shown to improve CR compared to standard dose daunorubucin 45mg/m2 in newly diagnosed AML patients. In our previous study, CR rate of induction with daunorubicin 60 mg/m2/d (3 days) and cytarabine 200 mg/m2/d days 1-7 was about 67%. Benefit of intensification seems limited to the patients without adverse cytogenetics. Wheher ultra high dose idarubicin 14mg/m2 (IA14) could further improve CR rate, give patients with adverse cytogenetics a chance to do allo-stem cell transplantation? This phase 2, prospective, single-center study is designed to evaluate the efficacy and safety of induction with idarubicin 14mg/m2/d (3 days) and cytarabine 200 mg/m2/d days 1-7 in young newly diagnosed AML patients.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Idarubicin and cytarabine induction

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xinxin Cao; Phone Number: 69155027; Email: caoxinxin@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100038
      • Recruiting
      • Xinxin Cao
      • Contact: Xinxin Cao; Email: caoxinxin@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome or a myeloproliferative neoplasm based on the World Health Organization (WHO) 2008 classification (at Screening)
• Must be competent and able to comprehend, sign, and date an Ethics Committee or Institutional Review Board approved Informed Consent Form (ICF) before performance of any study-specific procedures or tests;
• ≥18 yearsand ≤60 years (at Screening);
• Eastern Cooperative Oncology Group performance status 0-2 (at Screening);
• Adequate renal function defined as: Creatinine clearance rate >50 mL/min, as calculated with the modified Cockcroft Gault equation;
• Adequate hepatic function defined as: Total serum bilirubin ≤1.5 × ULN; and serum alkaline phosphatase, aspartate transaminase and alanine transaminase ≤2.5 × ULN;
• Serum electrolytes within normal limits: potassium, calcium (total or corrected for serum albumin in case of hypoalbuminemia). If outside of normal limits, subject will be eligible when electrolytes are corrected;

Exclusion Criteria:

• Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12); subjects who undergo diagnostic workup for APL and treatment with all-trans retinoic acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must be discontinued before starting induction chemotherapy).

• Prior treatment for AML, except for the following allowances:

  1. Leukapheresis;
  2. Treatment for hyperleukocytosis with hydroxyurea;
  3. Growth factor/cytokine support;

• Uncontrolled or significant cardiovascular disease, including any of the following:

  1. Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;
  2. Diagnosis of or suspicion of long QT syndrome (including family history of long QT syndrome);
  3. Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg;
  4. History of clinically relevant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes);
  5. History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker);
  6. History of uncontrolled angina pectoris or myocardial infarction within 6 months prior to Screening;
  7. History of New York Heart Association Class 3 or 4 heart failure;
  8. Complete left bundle branch block;
  9. Known history of left ventricular ejection fraction (LVEF) ≤45% or less than the institutional lower limit of normal;
• Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;
• Concurrent of other malignancies, except adequately treated non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease
• Females who are pregnant or breastfeeding;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IA14; Idarubicin 14mg/m2 for 3 days cytarabine 100mg/m2 every 12 hour for 7 days	Drug: Idarubicin and cytarabine induction; Idarubicin 14mg/m2 for 3 days cytarabine 100mg/m2 every 12 hour for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission (CR) rate	the rate of patient who get CR after induction therapy	On Day 21 (window Day 21 to Day 30), a bone marrow aspirate specimen will be collected for pathology.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	EFS is defined as the duration from initiation of IA induction treatment to the date of a first event	Assessed up to 24 months. Event is defined as any of the following: 1)Refractory disease (or treatment failure) which is determined at the end of the Induction Phase; 2)Relapse after CR or CRi; 3)Death from any cause at any time during the study.
Overall survival (OS)	OS was defined as the duration from initiation of IA induction treatment to the date of death or last follow-up	OS was defined as the duration from initiation of IA induction treatment to the date of death or last follow-up assessed up to 24 months.
rate of Minimal Residual Disease (MRD) negativity	Percentage of subjects achieving CR with no evidence of Minimal Residual Disease (MRD) following induction therapy.	MRD will be tested after on Day 21 (window Day 21 to Day 30)

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Jian Li, M.D., Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2019
• Primary Completion (Anticipated): October 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: August 22, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; induction; ultra-high dose idarubicin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cytarabine; Idarubicin
• Other Study ID Numbers: AML-IA14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No