Potential of asciminib in early chronic‑phase CML
Asciminib as Single Agent or in Combination With Nilotinib in the 1st-line Treatment of BCR-ABL1+ Chronic Myeloid Leukemia: a Randomized GIMEMA-GELMC Phase II Study PEARL Study: PotEntial of Asciminib in the eaRly Treatment of CML
This trial will see if asciminib alone, or asciminib plus nilotinib, helps adults newly diagnosed with chronic‑phase, BCR‑ABL–positive CML reach deep molecular responses and remain off treatment.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 160 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Gruppo Italiano Malattie EMatologiche dell'Adulto Academic / other |
| Drugs / interventions | asciminib, nilotinib |
| Locations | 11 sites (Barcelona and 10 other locations) |
| Trial ID | NCT06409936 on ClinicalTrials.gov |
What this trial studies
PEARL is a randomized, open‑label phase 2 study in adults with newly diagnosed chronic‑phase BCR‑ABL–positive CML comparing asciminib single‑agent (80 mg once daily) versus asciminib plus nilotinib (asciminib 40 mg twice daily plus nilotinib 300 mg twice daily after an initial period). Patients receive at least two years of treatment (core phase), followed by a two‑year consolidation phase with continued asciminib and reduced nilotinib dosing in the combination arm. Patients who maintain a stable deep molecular response (MR4) through year four may stop therapy and enter a treatment‑free remission (TFR) phase, with the proportion maintaining TFR assessed at five years. Disease is monitored by quantitative PCR throughout the study to guide dose adjustments and discontinuation decisions.
Who should consider this trial
Good fit: Ideal candidates are adults (≥18) with newly diagnosed chronic‑phase, Ph+/BCR‑ABL1+ CML within three months of diagnosis, typical e13a2 or e14a2 transcripts, limited prior TKI exposure (≤30 days), and adequate organ function.
Not a fit: Patients in advanced phases of CML, those with nonstandard BCR‑ABL transcripts, significant organ dysfunction, extensive prior TKI therapy, or inability to comply with long‑term follow‑up are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the regimen could increase rates of deep molecular response and allow more patients to attempt and maintain treatment‑free remission.
How similar studies have performed: Asciminib has shown clear activity in resistant or intolerant CML and nilotinib is an effective frontline TKI, but using asciminib frontline or combined with nilotinib in newly diagnosed patients is a relatively new approach with limited published frontline data.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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
Where this trial is running
Barcelona and 10 other locations
- 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)
Study contacts
- Principal investigator: Fausto Castagnetti — "Seragnoli" Institute of Hematology Bologna (Italy)
- Study coordinator: Paola Fazi
- Email: p.fazi@gimema.it
- Phone: 0670390528
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.