Phase III Trial in Acute Promyelocytic Leukemia Patients

• Status: Unknown status
• Trial end date: 2018-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Open label, randomised, phase III multicenter trial.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Collaborator: Study Alliance Leukemia (SAL) Group
• Treatments: 6-Mercaptopurine; Arsenic Trioxide; Idarubicin; Mercaptopurine; Methotrexate; Tretinoin

Criteria

Inclusion criteria

• Signed written informed consent according to IGH/EU/GCP and national local laws

• Newly diagnosed APL by cytomorphology, confirmed also by molecular analysis*.

• Age ≤18 < 71 years

• WHO performance status 0 -2 included

• WBC at diagnosis ≤ 10 x 109/L

• Serum total bilirubin ≤ 3.0 mg/dL (≤ 51µmol/L)

• Serum creatinine ≤ 3.0 mg/dL (≤ 260 µmol/L)

The confirmation of diagnosis at genetic level (microspeckled PML nuclear distribution by PGM3 monoclonal antibody and/or PML/RARa fusion by RT-PCR and/or demonstration of t(15;17) by karyotyping) will be mandatory for patient eligibility. However, in order to avoid delay in treatment initiation, patients can be randomised on the basis of morphologic diagnosis only and before the results of genetic tests are available.

Exclusion criteria

• Age < 18 and ≥ 71

• WBC at diagnosis > 10 x 109/L

• Other active malignancy at time of study entry

• Lack of diagnostic confirmation at genetic level

• Significant arrhythmias, EKG abnormalities (*see below) or neuropathy

• Other cardiac contraindications for intensive chemotherapy (L-VEF <50%)

• Uncontrolled, life-threatening infections

• Severe non-controlled pulmonary or cardiac disease

• Women who are either pregnant or breast feeding, or of child-bearing potential, defined as all women physiologically capable of becoming pregnant, UNLESS they meet one of the following definitions:

• Amenorrhea;

• post surgical bilateral oophorectomy with or without hysterectomy;

• using a highly effective method of birth control (defined as those which result in a failure rate less than 1% per year) when used consistently and correctly such as implants, injectables, oral contraceptives, IUDs, sexual abstinence or vasectomized partner.

• Concomitant severe psychiatric disorder

• HIV positivity

*EKG abnormalities:

• Congenital long QT syndrome;

• History or presence of significant ventricular or atrial tachyarrhythmia

• Clinically significant resting bradycardia (<50 beats per minute)

• QTc > 450 msec on screening EKG (using the QTcF formula detailed on page 18)

• Right bundle branch block plus left anterior hemiblock, bifascicular block

• Use of other investigational drugs at the time of enrolment or within 30 days before study entry