2nd or 3rd TKI-stop After 2 Years Nilotinib Pre-treatment in CML-patients

NCT02917720 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: ELN-0022015-004998-33
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 15

Brief Summary

The main goal of the study is the assessment of duration of major molecular response (MMR) or better at 12 and 36 months after stopping tyrosine kinase inhibitors (TKI) therapy a second or third time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 (BCR-ABL ratio \<0,01% on international Scale (IS) for at least one year and MR4.5 (BCR-ABL ratio \<0,0032% on IS) for at least 6 months:

• who failed a first stop in the EURO-SKI study (standardized criteria)
• who failed a first or second stop outside the EURO-SKI study but would have had fulfilled same eligible criteria and were stopped according to EURO-SKI rules
• who failed a first or second stop outside the EURO-SKI study without fulfilling EURO-SKI rules

Conditions

Chronic Myeloid Leukemia

Keywords

TKI discontinuation

Outcome Measures

Primary Outcomes (1)

• Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second or third time

  Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 for at least one year and MR4.5 for at least 6 months

  12 months after stopping

Secondary Outcomes (9)

• Assessment of quality of life (QoL) profiles under nilotinib treatment and comparison with previous TKI therapy before switch and after stopping

  5 years

• Identification of clinical and biological factors correlating with the persistence of MMR or better after stopping TKI

  6 months after stopping

• Estimation of overall survival

  3 years

• Time to re-achievement of MR4.5 after restart of therapy

  3 years

• Number of patients with grade 1 through grade 5 adverse events (AEs) that are related to study drug, graded according to NCI CTCAE Version 3.0

  3 years

Study Arms (1)

TKI-stop, pre-treatment with nilotinib

EXPERIMENTAL

Treatment after unsuccessful 1st or 2nd discontinuation at least two year with nilotinib (300 mg/bid). In total, retreatment with TKI for at least 3 years before entering screening for stopping phase is warranted. Clinical monitoring every 3 months during this 2 years. Patients who re-achieved and maintained MR4 for at least 12 months and MR4.5 for at least 6 months can enter screening phase for TFR .If MR4.5 is confirmed by an validated laboratory, patient may enter stopping phase of the study. Patient not fulfilling these criteria can be screened again every 3 months until month 48. After TKI-stop hematological monitoring and quantitative PCR of BCR/ABL1 (month 1-6 after stopping: monthly; month 7-12 after stopping: every 1.5 months, thereafter once every three months, for 3 years in total. Relapse is defined as BCR-ABL1 \> 0.1% on IS at a single time point (loss of MMR) In case of relapse restart of TKI. In general, the same TKI (nilotinib) as before second stop is recommended

Other: TKI discontinuation; Drug: nilotinib

Interventions

TKI discontinuation OTHER

2nd or 3rd TKI stop after pre-treatment with nilotinib.

TKI-stop, pre-treatment with nilotinib

nilotinib DRUG

Pre-treatment with nilotinib 300 mg/bid for 2 years

TKI-stop, pre-treatment with nilotinib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Patients with Ph chromosome and/or the BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML
• CML in CP having failed a prior attempt to stop imatinib or other TKIs therapy either within EURO-SKI or not
• Pretreatment at least one year with any TKI after 1st stop
• Written informed consent

You may not qualify if:

• Previous hematological relapse after first stop of TKI.
• Failure to any TKI at any time during CML treatment according to current ELN criteria
• Previous planned or performed allo SCT
• Previous AP/BC at any time in the history of the disease
• High cardiac risk according to ESC score (≥ 10 Points)
• Impaired cardiac function including any of the following:
• Use of a ventricular paced pacemaker; congenital long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant resting bradycardia (\<50 bpm); QTcF \>450 msec at baseline, myocardial infarction before baseline; other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension).
• Treatment with inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval is contraindicated.
• History of acute pancreatitis within one year of study entry or medical history of chronic pancreatitis.
• Positive hepatitis B virus serology test or HBV infection
• Any other malignancy except if neither clinically significant nor requires active intervention.
• Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, acute or chronic liver disease, pancreatic, or severe renal disease unrelated to tumor, active or uncontrolled infection).
• Women who are pregnant, breast feeding, or of childbearing potential without a negative serum pregnancy test at baseline. Male or female patients of childbearing potential unwilling to use an effective barrier contraceptive method

Sponsors & Collaborators

• European LeukemiaNet: lead
• Heidelberg University: collaborator
• Ludwig-Maximilians - University of Munich: collaborator

Study Sites (15)

Universitätsklinikum Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, 79108, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Klinikum rechts der Isar

München, Bavaria, 81675, Germany

Location

Medizinische Hochschule Hannover

Hannover, North Rhine-Westphalia, 30625, Germany

Location

Universitätsklinikum der RWTH

Aachen, 52074, Germany

Location

Klinikum Bayreuth

Bayreuth, 95445, Germany

Location

Klinikum Chemnitz

Chemnitz, 09113, Germany

Location

Onkologische Schwerpunktpraxis

Esslingen am Neckar, 73728, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

Schwerpunktpraxis Onkologie

Heilbronn, 74072, Germany

Location

Klinikum der Philipps-Universität

Marburg, 35033, Germany

Location

Kliniken Ostalb, Stauferklinikum Schwäbisch Gmünd

Mutlangen, 73557, Germany

Location

Universitätsklinikum Rostock

Rostock, 18057, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, 78052, Germany

Location

Amsterdam UMC, locatie VUmc

Amsterdam, 1081 HV, Netherlands

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

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

• Susanne Geiselhart

  Heidelberg University

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: March 2, 2016
• First Posted: September 28, 2016
• Study Start: September 1, 2016
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DE (14)