AITIK-Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Poitiers

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

5 Jul 2023 → ongoing

Decision date (initial)

2024-08-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CHU de Poitiers · GIRCI SOHO

External identifiers

EU CT number

2024-515479-36-00

EudraCT number

2022-004165-20

ClinicalTrials.gov

NCT05753384

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Therapy

To compare 2 TKI discontinuation strategies on the probability of successful discontinuation in patients followed for CML treated with TKIs.

Secondary objectives 9

1. 1.2-Comparison of TKI tolerability and quality of life in 2 arms
2. 3.4-Comparison of the proportion to loose MMR and DMR in 2 arms
3. 5-Comparison of the quantitative and qualitative evolution of CD8i LT in 2 arms
4. 6-Evaluate residual plasma TKI concentration for 2 arms
5. 7-Comparison of the proportion of loss DMR during the discontinuation phase in 2 arms
6. 8-Evaluate quality of life in the discontinuation phase in 2 arms
7. 9-Describe for patients losing their DMR in the TKI phase and for patients losing their MMR during the discontinuation phase
8. 10-Evaluate the predictive value at the time of discontinuation of the quantitative and qualitative characteristics of CD8LTi on the successful discontinuation between in TFR 24M post discontinuation and those who lost their MMR and resumed their TKI during the same period in 2 arms
9. 11-Analyse longitudinally the quantitative and qualitative evolution of CD8ILT after TKI discontinuation in patients in FIT 24M post discontinuation in 2 arms

Conditions and MedDRA coding

Chronic Myeloid Leukemia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Patient aged ≥ 18 years
2. Diagnosed with chronic phase CML (CML-CP) according to WHO 2016 criteria with a typical BCR::ABL1 rearrangement (e13a2/b2a2 or e14a2/b3a2)
3. Duration Imatinib ≥ 4 years/ TKI2G ≥ 3 years / Imatinib + ITK2G ≥ 4 years and not having had a dose reduction in the last 6 months
4. Duration of DMR (≥ 4-log reduction in peripheral blood BCR::ABL1 mRNA level from diagnosis) ≥ 1 year
5. No contraindication to the continuation of the same TKI for 12 months at the same dosage according to international recommendations and the originator's CPR of each TKI i.e.: Glivec® or generic: Imatinib (≥ 300 mg/d) Sprycel® or generic: Dasatinib (≥ 50 mg/d) Tasigna®: Nilotinib (≥ 300 mg/d) Bosulif®: Bosutinib (≥ 200 mg/d)
6. Sexually active men should use contraception while taking Dasatinib
7. Must be affiliated to the social security system or have a third party who does so
8. Patient not participating in another interventional study for the duration of the study
9. Have signed the consent form after having read the information note

Exclusion criteria 8

1. Patients with a serious progressive disease with poor prognosis compromising participation in the entire study and/or with an uncontrolled chronic disease (cardiac, (recent myocardial infarction, congestive heart failure, unstable angina...), renal, respiratory...)
2. ECOG > 3
3. Previous resistance to a TKI
4. Patients who have already involving a TKI discontinuation strategy
5. Patients with a malignant tumour that has been treated with chemotherapy in the 2 months prior to inclusion or is currently undergoing chemotherapy or will be treated with chemotherapy after inclusion
6. Persons benefiting from enhanced protection, i.e. minors, persons deprived of their liberty by a judicial or administrative decision, persons staying in a health or social establishment, adults under legal protection and finally patients in emergency situations
7. Pregnant or breastfeeding women, women of childbearing age who do not have effective contraception (hormonal/mechanical: per os, injectable, transcutaneous, implantable, intrauterine device, or surgical: tubal ligation, hysterectomy, total oophorectomy)
8. Patients who lost their DMR at the inclusion visit (i.e. BCR::ABL1/ABL1 ratio > 0.01%)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion (%) of patients in TFR 24 months after discontinuation in the dose maintenance then discontinuation arm and in the dose deescalation then discontinuation arm.

Secondary endpoints 9

1. 1-Recording of adverse events and scoring according to CTCAE V5 grades
2. 2.8-Collection of EQ-5D5 and FACT-Leu32
3. 3-Proportion (%) of patients losing their MMR
4. 4.7-Proportion (%) of patients losing their DMR
5. 5-Quantitative analysis: difference in the proportions, at randomisation and 12 months post-randomisation, of innate CD8 LTs within total CD8 LTs
6. 6-Evaluation of the residual plasma concentration of the TKI in ng/mL
7. 9-After loss of DMR during the treatment phase: collection of the prescribed TKI and its daily dosage (mg per day) as well as the time (in months) between the loss of DMR and its re-obtainment; after loss of MMR during the discontinuation phase: collection of the time (in months) between the loss of MMR and its re-obtainment
8. 10- Quantitative analysis: proportions of CD8i LTs in total CD8 LTs
9. 11- Quantitative analysis: proportions of innate CD8 LTs in total CD8 LTs

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Poitiers

Sponsor organisation

Centre Hospitalier Universitaire De Poitiers

Address

2 Rue De La Miletrie

City

Poitiers

Postcode

86000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Dr Emilie CAYSSIALS

Public contact point

Organisation

Centre Hospitalier Universitaire De Poitiers

Contact name

Dr Emilie CAYSSIALS

Locations

1 EU/EEA country · 20 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 15 files

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

Application history

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