DANTE = De-escalation and TFR Study in CML Patients Treated With Nilotinib Followed by a Second Attempt After Nilotinib and Asciminib Combination [Italy]
Type of study
Treatment discontinuation trial
Phase
Current status
Recruiting
Study title
DANTE (CAMN107AIT15) = A study of full treatment-free remission in patients with chronic myeloid leukemia treated with nilotinib
Scientific title
A Phase II, Single-arm Study of De-escalation and Treatment-free Remission in Patients With Chronic Myeloid Leukemia Treated With Nilotinib in First-line Therapy Followed by a Second Attempt After Nilotinib and Asciminib Combination: DANTE Study
Other trial ID
CAMN107AIT15, ClinicalTrials.gov NCT03874858, EudraCT 2018-002898-21
What is the purpose of the study
This study consists of two stages: Treatment-Free Remission 1 (TFR1) and Treatment-Free Remission 2 (TFR2).
The purpose of the TFR1 stage is to assess the effect of first-line treatment with half the standard dose of nilotinib (300 mg once daily) for 12 months on TFR in patients with Chronic Myeloid Leukemia in chronic phase (CML-CP) who reached a sustained deep molecular response (DMR) 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 to discontinue TKI and achieve TFR can lead to higher and more durable TFR rates after a second attempt than those reported in other studies.
What will happen during the study
The study consists of 4 phases: screening, 48-week nilotinib consolidation phase, 96-week treatment-free remission (TFR) phase and follow up phase.
During the TFR1 stage, all patients will be treated with nilotinib 300 mg once daily for up to 48 weeks. This is the so-called consolidation period.
- Patients with sustained DMR at the end of the consolidation period will enter the TFR1 stage, and nilotinib will be discontinued.
- Patients with loss of major molecular response (MMR) will be restarted on treatment with the standard dose of nilotinib (300 mg twice daily).
- Patients with MMR or better, but without sustained DMR at the end of the consolidation period will be treated with nilotinib 300 mg once daily.
Patients who lose MMR at any time during the study will be restarted on nilotinib treatment at 300 mg twice daily.
During the TFR2 stage, patients will be treated with nilotinib and asciminib for up to 96 weeks. This is the so-called the reintroducation period.
Key inclusion criteria
In TFR1 stage, this study includes male or female patients who:
- are aged 18 years or older
- have been diagnosed with CML in chronic phase according to the World Health Organization (WHO)
- have been receiving first line treatment with nilotinib at 300 mg twice daily for at least 3 calendar years.
At study entry, an ongoing treatment at a dose of 400 mg o rmore per day is allowed. - have had sustained deep molecular remission (MR4 or better with BCR-ABL results of no more than 0.01% on the international scale (IS) in the last 4 real time quantitative polymerase chain reaction (RQ-PCR) tests which were done at least 3 months but no more than 6 months apart.
- have acceptable laboratory values at screening
- have an Eastern Co-Operative Oncology Group (ECOG) status of 0, 1 or 2.
In TFR2 stage, this study includes male or female patients who:
- are aged 18 years or older.
- have been diagnosed with CML in chronic phase according to the WHO and have no previous history of progression to AP/BP CML.
- have been receiving first line treatment with nilotinib for at least 3 calendar years, followed by a first TFR attempt
- have failed a first TFR attempt followed by at least 1 year of nilotinib retreatment before enrollment in TFR2 stage.
- who have been in MR4 or better (with BCR-ABL results of no more than 0.01% IS) at screening.
Further criteria may apply. Please discuss these with your doctor or study staff.
Key exclusion criteria
In TFR1 stage, this study does not include patients who:
- have a known atypical transcript
- have CML treatment resistant mutation(s) that were detected in the past
- reduced or interrupted their doses due to neutropenia or thrombocytopenia in the past 6 months
- have attempted to permanently stop taking nilotinib.
In TFR2 stage, this study does not include patients who:
- have a known atypical transcript
- have CML treatment resistant mutation(s) that were detected in the past
- reduced or interrupted their doses due to neutropenia or thrombocytopenia in the past 6 months
Further criteria may apply. Please discuss these with your doctor or study staff.
Estimated primary completion date
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.
You can also find a study description in the EU Clinical Trials Register. This is a database hosted by the European Medicines Agency (EMA).
Study sponsor
Novartis Pharmaceuticals
Scientific lead / contact
Novartis Pharmaceuticals
Principal investigator
Novartis Pharmaceuticals
Study centers / principal investigators
Italy
Novartis Investigative Site
Bari, 70124
Novartis Investigative Site
Bologna, 40138
Novartis Investigative Site
Cagliari, 09126
Novartis Investigative Site
Catania, 95123
Novartis Investigative Site
Catanzaro, 88100
Novartis Investigative Site
Firenze, 50134
Novartis Investigative Site
Genova, 16132
Novartis Investigative Site
Milano, 20122
Novartis Investigative Site
Milano, 20162
Novartis Investigative Site
Napoli, 80131
Novartis Investigative Site
Napoli, 80132
Novartis Investigative Site
Novara, 28100
Novartis Investigative Site
Orbassano, 10043
Novartis Investigative Site
Palermo, 90127
Novartis Investigative Site
Palermo, 90146
Novartis Investigative Site
Pescara, 65124
Novartis Investigative Site
Perugia, 06100
Novartis Investigative Site
Pisa, 56126
Novartis Investigative Site
Ravenna, 48100
Novartis Investigative Site
Reggio Emilia, 42123
Novartis Investigative Site
Roma, 00144
Novartis Investigative Site
Roma, 00161
Novartis Investigative Site
Roma, 00168
Novartis Investigative Site
Salerno, 84131
Novartis Investigative Site
Siena, 53100
Novartis Investigative Site
Torino, 10126
Novartis Investigative Site
Torino, 10128
Novartis Investigative Site
Udine, 33100
Novartis Investigative Site
Verona, 37126