HALF = Efficacy and safety of TKI withdrawal after a two-step dose reduction in patients with CML [Czechia]

Study title

HALF = Efficacy and safety of TKIs‘ withdrawal after a two-step dose reduction in patients with chronic myeloid leukemia (CML)

Scientific title

A prospective phase II clinical trial evaluating the efficacy and the safety of tyrosine kinase inhibitors withdrawal after a previous two-step dose reduction in patients with chronic myeloid leukemia in deep molecular remission

Type of study

Treatment discontinuation trial

Phase

2

Current status

Active, not recruiting

Other trial ID

HALF2019, ClinicalTrials.gov NCT04147533

What is the purpose of the study

This study will evaluate the safety and efficacy of stopping treatment with a tyrosine kinase inhibitor (TKI) (imatinib, dasatinib or nilotinib) in patients with CML in deep molecular remission.

What will happen during the study

The dose of the TKI will be reduced in two steps: during the first 6 months after study entry by 50% of standard dose; during the second 6 months this already reduced dose will be given every other day; the medication is discontinued then and the patients are followed every month in the first 6 months after withdrawal, every 1.5 month in the next 6 months, and every 3 months in the next 12 months.

Key inclusion criteria

This study includes male or female patients who:

  • are aged 18 years or older
  • have a documented diagnosis of Philadelphia chromosome-positive (Ph1) and/or BCR-ABL1-positive CML in a documented first chronic phase, as defined in the study protocol
  • have a typical [e13a2 (b2a2) or e14a2 (b3a2)] or atypical quantifiable type of BCR-ABL1 transcript on an international scale (IS)
  • have been treated with a tyrosine kinase inhibitor (TKI) either in the first line, or in the second or other lines for intolerance only
  • have been receiving a TKI for more than 4 years
  • have been in deep molecular response, defined as MR4.0 or better, for more than 2 years.

Further criteria may apply. Please discuss these with your doctor or study staff.

Key exclusion criteria

This study does not include patients who:

  • have had Ph1-positive and / or BCR-ABL1-positive CML in the second chronic phase, in the accelerated phase or blast crisis (AP/BC) at any time in the history of the disease
  • have a type of BCR-ABL1 transcript that cannot be quantified on an international scale
  • have been treated with a TKI in the second or later lines due to treatment failure according to ELN (European LeukemiaNet) criteria in 2006, 2009 or 2013
  • have failed TKI treatment according to ELN criteria of 2006, 2009 or 2013
  • previously underwent allogeneic hematopoietic stem cell transplantation
  • previously participated in a TKI withdrawal study with a real withdrawal history
  • previously discontinued TKI treatment outside the study for other reasons (eg intolerance or pregnancy) lasting more than 9 months and / or if a treatment response was lost during less than 12 months prior to screening.

Further criteria may apply. Please discuss these with your doctor or study staff.

Estimated primary completion date

December 2025

Where can I find additional information

You can find a study description in the US register ClinicalTrials.gov. This is a database provided by the U. S. National Institutes of Health.

 

Study sponsor

Masaryk University
Žerotínovo náměstí 617/9
601 77 Brno
Czech Republic

Scientific lead / contact

Daniela Zackova, MD, PhD
Dpt. of Internal Medicine Hematology and Oncology
University Hospital Brno
Jihlavska 20
625 00 Brno
Czech Republic
Tel.: +420 53223 3642
E-mail: zackova.daniela@fnbrno.cz

Principal investigator

Daniela Zackova, University Hospital Brno

Study centers / principal investigators

Czechia

University Hospital Brno
Brno, 62500

University Hospital Hradec Kralove
Hradec Králové, 50005

University Hospital Olomouc
Olomouc, 77900

University Hospital Ostrava
17. listopadu 1790/5
Ostrava, 70852
Principal Investigator: Lukas Stejskal, MD

University Hospital Plzen
Plzen, 30599

University Hospital Kralovske Vinohrady
Praha 10, 10034

Insitute of Hematology and Blood Transfusion
Praha 2, 12800

General University Hospital in Prague
Praha 2, 12808