Sustained Treatment-free Remission in BCR-ABL+ Chronic Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2024-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The study will investigate in newly diagnosed CP-CML patients the efficacy of NIL frontline therapy vs IM followed by switch to NIL in the case of absence of optimal response as defined by the ELN criteria.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Treatments: Imatinib Mesylate

Criteria

Inclusion Criteria:

• Patients with a confirmed diagnosis of BCR/ABL+ CML in chronic phase

Documented chronic phase CML must meet all the following criteria:

< 15% blasts in peripheral blood < 30% blasts plus promyelocytes in peripheral blood < 20% basophils in the peripheral blood

• 100 x 109/L (≥ 100,000/mm3) platelets

• Age ≥18

• ECOG performance status of 0-2

• Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR

• Adequate end organ function as defined by:

Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab).

Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert's disease) grade < 3 SGOT (AST) and SGPT (ALT) ≤ 3 x ULN Serum amylase and lipase ≤ 2 x ULN Alkaline phosphatase ≤ 2.5 x ULN Serum creatinine < 1.5 x ULN

• Having completed the QoL baseline evaluation (i.e., before randomization)

• Written informed consent prior to any study procedures.

Exclusion Criteria:

• Expression of any atypical BCR-ABL transcripts, instead of the classical P210-encoding type with the e13a2 or the e14a2 junction at screening.

• Previous treatment with BCR-ABL inhibitors for a period longer than 1 month.

• Previous anticancer agents (hydroxyurea, anagrelide, interferon) for CML for a time longer than three months.

• Poorly controlled diabetes mellitus (defined as HbA1c >8%).

• Prior documented history of coronary heart disease, including myocardial infarction, coronary bypass, coronary stent, and symptomatic angina:

LVEF <45% or below the institutional lower limit of the normal range (whichever ishigher) Complete left bundle branch block Right bundle branch block plus left anterior or posterior hemiblock Use of a ventricular-paced pacemaker Congenital long QT syndrome or a known family history of long QT syndrome History of or presence of clinically significant ventricular or atrial tachyarrhythmias

• Atrial fibrillation or flutter

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

• QTc > 450 msec on the average of three serial screening ECGs (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and the patient re-tested History or clinical signs of myocardial infarction within 12 months of study entry History of unstable angina within 12 months of study entry Other clinically significant heart disease (e.g. congestive heart failure)

• Uncontrolled hypertension is not a heart disease.

• History of peripheral arterial occlusive disease.

• History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis.

• Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug.

• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which cannot be either safely discontinued or switched to a different medication prior to starting study drug.