A Study of REduction And DIscontinuation Treatment of TKI (Imatinib, Nilotinib, Dasatinib and Bosutinib)

NCT ID: NCT04578847

Last Updated: 2020-10-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-15
• Study Completion Date: 2025-01-15

Brief Summary

The main goal of this study is to evaluate the stability of molecular response (major and deep molecular response( MMR and DMR)) in patients with chronic myeloid leukemia (CML) with stable DMR after two-stage dose reduction phase and discontinuation treatment TKI: imatinib, nilotinib, dasatinib and bosutinib.

Detailed Description

The duration of the dose reduction phase will be 12 months. This phase will have two stage of 6 months, respectively.

The dose of imatinib, nilotinib, dasatinib or bosutinib will be reduced by 25-50% on the first stage, and by another 25% on the second stage.

• The initial dose of imatinib will be 400 mg daily. The dose will be reduced by 300 mg daily on the first stage, by 200 mg daily - on the second stage.
• The initial dose of nilotinib will be 300 or 400 mg twice daily. The dose will be reduced by 400 mg daily on the first stage, by 200 mg daily - on the second stage.
• The initial dose of dasatinib will be 100 or 140 mg daily. The dose will be reduced by 50 mg daily on the first stage, by 25 mg daily - on the second stage.
• The initial dose of bosutinib will be 500 mg daily. The dose will be reduced by 300 mg daily on the first stage, by 200 mg daily - on the second stage.

All patients with stable deep molecular response (at least 2 years) will be included in treatment free remission phase (TFR-phase). The duration of TFR-phase will be 24 months.

The CML patients can enter the study already on reduced doses TKI, if they will meet the inclusion criteria.

It is possible to include patients, who have already received therapy with reduced doses of TKI. The duration of TKI therapy with reduced doses of 1 stage should be at least 6 months, if TKI doses meet of stage 1. The duration of TKI therapy with reduced doses of 2 stage should be for at least 6 months and the general duration of TKI therapy with reduced doses should be for at least 12 months, if TKI doses meet of stage 2.

Conditions

Chronic Myeloid Leukemia; Chronic Myeloid Leukemia in Remission; BCR-ABL Positive Chronic Myelogenous Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

The TKI dose reduction

Imatinib, nilotinib, dasatinib or bosutinib; the two stage of TKI dose reduction phase for 12 months (6 months and 6 months, respectively).

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: DRUG

Initial dose - 400 mg daily. If on imatinib, the dose should be decreased to 300 mg daily on the first stage, to 200 mg daily - on the second stage.

Nilotinib

Intervention Type: DRUG

Initial dose - 300 or 400 mg twice daily. If on nilotinib to 400mg daily on the first stage, to 200 mg daily - on the second stage.

Dasatinib

Intervention Type: DRUG

Initial dose 100 or 140 mg daily. If on dasatinib then to 50 mg daily on the first stage, to 25 mg daily - on the second stage.

Bosutinib

Intervention Type: DRUG

Initial dose 500 mg daily. If on bosutinib, the dose should be reduced to 300 mg daily on the first stage, to 200 mg daily on the second stage.

Interventions

Imatinib

Initial dose - 400 mg daily. If on imatinib, the dose should be decreased to 300 mg daily on the first stage, to 200 mg daily - on the second stage.

Intervention Type: DRUG

Nilotinib

Initial dose - 300 or 400 mg twice daily. If on nilotinib to 400mg daily on the first stage, to 200 mg daily - on the second stage.

Intervention Type: DRUG

Dasatinib

Initial dose 100 or 140 mg daily. If on dasatinib then to 50 mg daily on the first stage, to 25 mg daily - on the second stage.

Intervention Type: DRUG

Bosutinib

Initial dose 500 mg daily. If on bosutinib, the dose should be reduced to 300 mg daily on the first stage, to 200 mg daily on the second stage.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. CML in chronic phase.

2. TKI treatment for at least 3 years.

3. DMR (BCR-ABL≤0.01%) for at least 1 year, MMR (BCR-ABL≤0.1%) for at least 2 years

4. At least 3 molecular results over the preceding 24 months, which confirm the presence of MMR and DMR

5. Written Informed Consent

6. CML patients with DMR for at least 1 years and MMR for at least 2 years after STOP TKI in anamnesis.

For patients who are on the reduced dose TKI (1 stage) at the time of inclusion in the study

1. The duration of therapy at reduced doses of TKI phase I is at least 6 months.

For patients on the reduced dose TKI (2 stage, before TFR phase) at the time of inclusion in the study

1. DMR (BCR-ABL≤0.01%) for at least 2 years

2. The duration of therapy at reduced doses of TKI phase 1 is for at least 6 months, the total duration of therapy at reduced doses is for at least 12 months.

Exclusion Criteria

1. Age under 18

2. ECOG >2

3. CML in accelerated phase or blast crisis at any time

4. Lack of Written Informed Consent

5. Pregnant or lactating women

6. Incapacity

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research Center for Hematology, Russia

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna Turkina, Professor

Role: PRINCIPAL_INVESTIGATOR

National Research Center for Hematology

Locations

National Research Center for Hematology

Moscow, , Russia

Countries

Russia

Other Identifiers

READIT-2020

Identifier Type: -

Identifier Source: org_study_id