PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML

NCT06409936 | Recruiting Phase 2 DMC

• 1 other identifier: CML1624
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 11

Brief Summary

A phase 2, interventional, randomized unblinded study will be conducted in newly diagnosed CP CML patients, to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent (arm A) or 40 mg BID in combination with nilotinib 300 mg BID (arm B). All patients in both arm A and arm B will be treated for a minimum of 2 years (core phase). If they will have achieved a DMR (MR4), or if it will be in the interest of the patient, the treatment will be continued. During the consolidation phase (2 years) asciminib will be continued at the same dose in both arms; in the combination arm the nilotinib dose will be reduced to 300 mg daily. The patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment (TFR phase). The rate of TFR at 5 year (1 year after discontinuation) will be evaluated.

Conditions

CML, Chronic Phase; Chronic Myeloid Leukemia, Chronic Phase; Chronic Myeloid Leukemia, BCR/ABL-Positive; Chronic Myeloid Leukemia

Keywords

asciminib; nilotinib

Outcome Measures

Primary Outcomes (1)

• evaluation of response of asciminib single-agent or in combination with nilotinib

  Rate of deep molecular response (MR4) achievement

  at 2 years

Study Arms (2)

Asciminib single agent

EXPERIMENTAL

Core phase (2 years): asciminib 80 mg QD will be given as single-agent. Consolidation phase (2 years): If patients will have achieved a DMR (MR4), or if it will be in their interest, the treatment will be continued with asciminib 80 mg QD. Treatment free remission phase (1 year): patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment

Drug: Asciminib

Asciminib plus nilotinib

EXPERIMENTAL

Core phase (2 years): asciminib 80 mg QD will be started, then after 90 days asciminib will be given 40 mg BID and nilotinib 300 mg BID, or 300 mg OAD according to the presence/absence of asciminib adverse events, will be added-on. Consolidation phase (2 years): If patients will have achieved a DMR (MR4), or if it will be in their interest, the treatment will be continued with asciminib 40 mg BID and nilotinib reduced to 300 mg daily. Treatment free remission phase (1 year): patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment

Drug: Asciminib; Drug: Nilotinib

Interventions

Asciminib DRUG

both arms will include asciminib treatment

Asciminib plus nilotinib; Asciminib single agent

Nilotinib DRUG

in the arm B the nilotinib will be added on in all patients

Asciminib plus nilotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytogenetic and molecular confirmed diagnosis of Ph+ and BCR::ABL1+ CML
• Age ≥ 18 years
• Early chronic phase, less than 3 months from diagnosis
• Evidence at the time of study entry of typical BCR::ABL1 RNA transcripts e13a2 or e14a2 (b2a2 or b3a2), which are required for BCR::ABL1 international scale reporting
• Prior treatment with any TKI for 30 days or less; prior treatment with hydroxyurea or anagrelide is allowed
• ECOG performance status of 0, 1 or 2
• Adequate end organ function as defined by Total bilirubin ≤ 1.5 x ULN except for patients with Gilbert's syndrome who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN Aspartate transaminase (AST) ≤ 3.0 x ULN Alanine transaminase (ALT) ≤ 3.0 x ULN Serum amylase ≤ ULN Serum lipase ≤ ULN Alkaline phosphatase ≤ 2.5 x ULN, unless considered tumor related Creatinine clearance \> 50 ml/min using Cockcroft-Gault formula
• Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedure
• An effective form of contraception with their sexual partners from enrolment through 30 days after the end of treatment

You may not qualify if:

• CML in blast phase (BP) or in second chronic phase after previous BP, according to WHO criteria
• Previous treatment with TKIs for more than 30 days
• Refusal or impossibility to give an informed consent
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following: recent myocardial infarction (within last 6 months), uncontrolled congestive heart failure, unstable angina (within last 6 months), clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
• Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection)
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
• History of acute or chronic liver disease
• History of other active malignancy within 2 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
• Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), or Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab / anti HBc) will be performed at study entry
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
• Pregnant or lactating women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after the end of treatment

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead
• Grupo Español de Leucemia Mieloide Crónica: collaborator

Study Sites (11)

Hospital del Mar (Barcelona)

Barcelona, Spain

RECRUITING

Hospital Universitario Basurto

Bilbao, Spain

RECRUITING

Institut Català d'Oncologia Girona

Girona, Spain

RECRUITING

Hospital Virgen de las Nieves

Granada, Spain

RECRUITING

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Spain

RECRUITING

Hospital Gral U. Gregorio Marañón

Madrid, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

RECRUITING

Complejo Asistencial Universitario de Salamanca

Salamanca, Spain

RECRUITING

Hospital Universitario La Fe Valencia

Valencia, Spain

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Fausto Castagnetti

  "Seragnoli" Institute of Hematology Bologna (Italy)

  PRINCIPAL INVESTIGATOR

• Valentin Garcia Gutierrez

  Hematology Unit, Hospital Universitario Ramón y Cajal, Madrid (Spain)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Fazi

CONTACT

0670390528; p.fazi@gimema.it

Enrico Crea

CONTACT

0670390514; e.crea@gimema.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 10, 2024
• Study Start: June 26, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2032
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

ES (11)