A Study of Full Treatment-free Remission in Patients With Chronic Myeloid Leukemia

NCT03874858 | Completed Phase 2

• 2 other identifiers: CAMN107AIT152024-516122-66-00
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 26

Brief Summary

This study is constituted of two stage: Treatment-Free Remission 1 (TFR1) stage and Treatment-Free Remission 2 (TFR2) stage. The purpose of the TFR1 stage is to assess the effect of nilotinib reduced to half the standard dose for 12 months on treatment-free remission in patients with Chronic Myeloid Leukemia - Chronic Phase (CML-CP) treated with first-line nilotinib who reached a sustained deep molecular response before entering the study. The purpose of the TFR2 stage is to evaluate whether the use of asciminib in combination with nilotinib after failure of a first attempt at TFR can lead to higher and more durable TFR rates after a second attempt at TKI discontinuation than those reported in other studies.

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic Myeloid Leukemia (CML); Chronic Myeloid Leukemia - Chronic Phase (CML-CP); Deep Molecular Response (DMR); sustained deep molecular response (sustained DMR); Treatment-Free Remission (TFR); Treatment-Free Remission failure (TFR failure); Full Treatment-Free Remission (FTFR); Tyrosine Kinase Inhibitor (TKI); quantitative Polymerase Chain Reaction (qPCR); digital droplet Polymerase Chain Reaction (ddPCR); ABL001 (Asciminib); AMN107 (Nilotinib); Tasigna; adult

Outcome Measures

Primary Outcomes (2)

• Percentage of patients in full treatment-free remission 96 weeks after the start of the consolidation period of TFR1 stage

  Full Treatment-Free Remission (FTFR) is defined as patients with Major Molecular Response (MMR) or better (i.e. BCR-ABL ≤ 0.1% IS), including those who have totally discontinued treatment during the Treatment-Free Remission (TFR) stage and those who are treated with half the standard dosage. Percentage of patients in full treatment-free remission 96 weeks after the start of the consolidation period of TFR1 stage is calculated by dividing the number of patients with no loss of MMR-Major Molecular Response (BCR-ABL ≤ 0.1% (IS) after 96 weeks by the number of patients who entered consolidation of TFR1 stage.

  Baseline of consolidation phase up to 96 weeks of TFR1 stage

• Percentage of patients in treatment-free remission 48 weeks after starting a second attempt at treatment-free remission during TFR2 stage.

  Treatment-Free Remission (TFR) is defined as patients with MMR or better (i.e. BCR-ABL ≤ 0.1% IS). Percentage of patients in TFR 48 weeks after the start of TFR2 phase during TFR2 stage is calculated by dividing the number of patients with no loss of MMR after 48 weeks by the number of patients who entered TFR2 during TFR2 stage. Patients who require re-initiation of nilotinib during TFR2 for loss of MMR, and those discontinued from the study will be considered failures.

  Baseline TFR2 phase (week 96 of TFR2 stage) up to week 144 of TFR2 stage

Secondary Outcomes (28)

• Percentage of patients who remain in sustained Deep Molecular Response (DMR) at the end of the consolidation period (week 48 TFR1 stage).

  Baseline of consolidation period up to 48 weeks (TFR1 stage)

• Percentage of patients who remain in DMR at the end of the consolidation period (week 48 of TFR1 stage), at 96 weeks and at 144 weeks after the start of the consolidation period of TFR1 stage.

  Baseline of consolidation period, week 48, week 96 and week 144 (TFR1 stage)

• Percentage of patients in full treatment-free remission 144 weeks after the start of consolidation ( end of the TFR1 stage.)

  Baseline of consolidation period, week 144 of TFR1 stage

• Percentage of patients with MMR or better at 48, 96, 144 weeks after starting the consolidation period of TFR1 stage

  Baseline of consolidation period, week 48, 96 and 144 of TFR1 stage

• Change in BCR-ABL transcript levels after re-start of nilotinib therapy in patients who failed Treatment Free Remission Phase during TFR1 stage.

  Restart of nilotinib therapy up to 144 weeks of TFR1 stage

Study Arms (2)

TFR1 stage- Nilotinib

EXPERIMENTAL

During TFR1 stage, all patients will be treated with nilotinib 300 mg QD for up to 48 weeks (consolidation period). * Patients with sustained DMR at the end of the consolidation period will enter the TFR1 period and nilotinib will be discontinued. * Patients with loss of MMR will return to the standard nilotinib administration * Patients with ≥ MMR, but without sustained DMR at the end of the consolidation period will be treated with nilotinib 300 mg QD

Drug: Nilotinib

TFR2 stage- Nilotinib+Asciminib

EXPERIMENTAL

During the TFR2 stage, participants will be treated with nilotinib and asciminib for up to 96 weeks (reinduction period). * Patients with sustained DMR at the end of reinduction will enter TFR2 and asciminib + nilotinib will be discontinued. * Patients with ≥ MMR, but without sustained DMR, at the end of the reinduction, will be treated with nilotinib monotherapy at 300 mg BID until the end of the TFR2 stage. * Patients with loss of MMR at any time during reinduction or during nilotinib monotherapy will be discontinued from the study.

Drug: Nilotinib; Drug: Asciminib

Interventions

Nilotinib DRUG

Nilotinib oral 300 mg QD hard capsules

Also known as: AMN107

TFR1 stage- Nilotinib

Asciminib DRUG

Asciminib orally at a dose of 40 mg BID film-coated tablets (FCT)

Also known as: ABL001

TFR2 stage- Nilotinib+Asciminib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients 18 years or older.
• Diagnosis of CML-CP according to the World Health Organization (WHO).
• Patients with CML-CP under first-line treatment with nilotinib at the approved daily dose of 300 mg BID mg for at least 3 calendar years.
• Note: At study entry, an ongoing treatment at a dose ≥400 mg per day is allowed.
• Sustained DMR defined as ≥ MR 4.0 (BCR-ABL level ≤0.01% IS) in all of the last 4 BCR-ABL RQ-PCR assessments with a minimum interval between each assessment of 3 months and a maximum interval of 6 months.
• Patient must meet the following laboratory values at the screening visit:
• Absolute Neutrophil Count ≥1.0 x 109/L
• Platelets ≥75 x 109/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Serum creatinine \< 1.5 mg/dL
• Aspartate transaminase (AST) ≤ 3.0 x ULN
• Alanine transaminase (ALT) ≤ 3.0 x ULN
• Serum lipase ≤ 2 x ULN
• Eastern Cooperative Oncology Group performance status (ECOG) 0-2.
• Study subjects must be able to comply with study procedures and follow-up examinations.

You may not qualify if:

• Patients with known atypical transcript.
• CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past).
• Dose reductions/interruptions due to neutropenia or thrombocytopenia in the past 6 months.
• Patient ever attempted to permanently discontinue nilotinib treatment.
• Known impaired cardiac function including any one of the following:
• Inability to determine QT interval on ECG
• Complete left bundle branch block
• Long QT syndrome or a known family history of long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia
• QTcF \> 480 msec
• History or clinical signs of myocardial infarction within 1 year prior to study entry
• History of unstable angina within 1 year prior to study entry
• Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension)
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (26)

Novartis Investigative Site

Bari, BA, 70124, Italy

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Cagliari, CA, 09121, Italy

Location

Novartis Investigative Site

Catania, CT, 95123, Italy

Location

Novartis Investigative Site

Catanzaro, CZ, 88100, Italy

Location

Novartis Investigative Site

Florence, FI, 50134, Italy

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Milan, MI, 20162, Italy

Location

Novartis Investigative Site

Palermo, PA, 90127, Italy

Location

Novartis Investigative Site

Palermo, PA, 90146, Italy

Location

Novartis Investigative Site

Pescara, PE, 65124, Italy

Location

Novartis Investigative Site

Perugia, PG, 06129, Italy

Location

Novartis Investigative Site

Pisa, PI, 56126, Italy

Location

Novartis Investigative Site

Reggio Emilia, RE, 42123, Italy

Location

Novartis Investigative Site

Roma, RM, 00144, Italy

Location

Novartis Investigative Site

Roma, RM, 00161, Italy

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Salerno, SA, 84131, Italy

Location

Novartis Investigative Site

Siena, SI, 53100, Italy

Location

Novartis Investigative Site

Orbassano, TO, 10043, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Torino, TO, 10128, Italy

Location

Novartis Investigative Site

Verona, VR, 37134, Italy

Location

Novartis Investigative Site

Naples, 80131, Italy

Location

Novartis Investigative Site

Novara, 28100, Italy

Location

MeSH Terms

Conditions

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

Interventions

nilotinib; asciminib

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

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 14, 2019
• Study Start: March 22, 2019
• Primary Completion: October 15, 2025
• Study Completion: October 15, 2025
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (26)