Study to treat adult patients with BCR-ABL1+ Chronic Myeloid Leukemia with Asciminib as single agent or in combination with nilotinib:a GIMEMA-GELMC phase II study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Gimema Franco Mandelli Onlus, Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

24 Jun 2025 → ongoing

Decision date (initial)

2025-04-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

NOVARTIS PHARMA AG · FONDAZIONE GIMEMA FRANCO MANDELLI ONLUS · GELMC ( GRUPO ESPAÑOL DE LEUCEMIA MIELOIDE CRÓNICA)

External identifiers

EU CT number

2024-512696-12-00

ClinicalTrials.gov

NCT06409936

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective is to assess the efficacy, in terms of achievement of DMR (MR4), of asciminib singleagent or in combination with nilotinib in the first-line treatment of patients with BCR::ABL1+ CML in early CP.

Secondary objectives 9

1. To assess the rate of treatment-free remission
2. to assess the molecular response at timepoints
3. to assess the dynamics of molecular response
4. to assess the survival outcomes
5. to evaluate baseline and response-related predictors of response
6. to assess the type and dynamics of emergent BCR::ABL1 mutations
7. to assess the type and dynamics of emergent cancer related somatic mutations
8. to assess the safety profile
9. to investigate HRQoL differences between treatment arms over time, up to 24 months.

Conditions and MedDRA coding

BCR-ABL1+ Chronic Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Cytogenetic and molecular confirmed diagnosis of Ph+ and BCR::ABL1+ CML
2. Age ≥ 18 years
3. Early chronic phase, less than 3 months from diagnosis
4. Evidence at the time of study entry of typical BCR::ABL1 RNA transcripts e13a2 or e14a2 (b2a2 or b3a2), which are required for BCR::ABL international scale reporting
5. Prior treatment with any TKI for 30 days or less; prior treatment with hydroxyurea or anagrelide is allowed
6. ECOG performance status of 0, 1 or 2
7. 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 ≤ 1.5 x ULN - Serum lipase ≤ 1.5 x ULN - Alkaline phosphatase ≤ 2.5 x ULN, unless considered tumor related - Creatinine clearance > 50 ml/min using Cockcroft-Gault formula
8. Signed written informed consent according to ICH/EU/GCP and national local laws prior to any study procedure
9. An effective form of contraception with their sexual partners from enrolment through 30 days after the end of treatment.

Exclusion criteria 12

1. CML in blast phase (BP) or in second chronic phase after previous BP, according to WHO criteria
2. Previous treatment with TKIs for more than 30 days
3. Refusal or impossibility to give an informed consent
4. 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).
5. 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)
6. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
7. History of acute or chronic liver disease
8. 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
9. 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
10. 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)
11. 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.
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the rate of deep molecular response (MR4) at 2 years; patients with not evaluable molecular analysis may repeat a QPCR analysis in 1 month (25 months from day 1)

Secondary endpoints 9

1. The rate of sustained MR4 or MR4.5 at 4 years (TFR eligibility) and the proportion of patients free from relapse (BCR::ABL1 transcript < 0.1%) 12 months after treatment discontinuation
2. The rate of major molecular response (MR3) at and by 1, 2, 3, 6, 12, 18 and 24 months, and the rate of MR4 and MR4.5 at and by 1, 2, 3, 4 years
3. The median time to response (MR3, MR4, MR4.5) and the relationship between the time to response (response at milestones) and the TFR eligibility at 4 years and the TFR rate 12 months after discontinuation
4. Outcome measures at 2 and 5 years: overall survival (OS), survival without leukemia-related death, progression-free survival (PFS)
5. Outcome measures at 5 years according to baseline prognostic factors (Sokal and ELTS score, CCA in Ph+ cells, BCR::ABL transcript type, and according to the early response (BCR::ABL transcript level at 3 and 6 months)
6. Incidence and VAF of treatment emergent BCR::ABL1 mutations
7. Incidence and VAF of BL and treatment emergent cancer related somatic mutations and relationship with treatment efficacy, including treatment-free remission and outcome
8. Incidence of hematologic and non-hematologic adverse events
9. Mean HRQoL scores trajectories by the EORTC QLQ-C30 and QLQ-CML24 questionnaires according to treatment arm

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Gimema Franco Mandelli Onlus

Sponsor organisation

Fondazione Gimema Franco Mandelli Onlus

Address

Via Casilina 5

City

Rome

Postcode

00182

Country

Italy

Scientific contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Data center

Public contact point

Organisation

Fondazione Gimema Franco Mandelli Onlus

Contact name

Data center

Third parties 2

Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

Sponsor organisation

Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

Address

Carre De Balmes 243 Escalera A 5º 1ª

City

Barcelona

Postcode

08006

Country

Spain

Scientific contact point

Organisation

Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

Contact name

SECRETARÍA TÉCNICA GELMC

Public contact point

Organisation

Grupo Espanol De Leucemia Mieloide Cronica (GELMC)

Contact name

SECRETARÍA TÉCNICA GELMC

Third parties 2

Sponsor responsibilities

Article 77 compliance

Fondazione Gimema Franco Mandelli Onlus

Contact point sponsor

Fondazione Gimema Franco Mandelli Onlus

Article 77 implementation

Fondazione Gimema Franco Mandelli Onlus

Locations

2 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications