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

Prospective Non-randomized Stratified Study of REduction And DIscontinuation Treatment of TKI (Imatinib, Nilotinib, Dasatinib and Bosutinib) in Adults With Ph+ Chronic Myeloid Leukemia With Stable Deep Molecular Response

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Myeloid Leukemia; Chronic Myeloid Leukemia in Remission; BCR-ABL Positive Chronic Myelogenous Leukemia
• Intervention / Treatment: Drug: Imatinib; Drug: Nilotinib; Drug: Dasatinib; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • National Research Center for Hematology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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).

Drug: 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.; 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.; 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival, survival without molecular relapse	37 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients with molecular relapse who achieved MMR and DMR after the resumption TKI therapy in standard doses		37 months
The proportion of patients who resolved the adverse events after TKI dose reduction and discontinuation of TKI therapy		37 months
The proportion of patients who have TKI withdrawal syndrome after TKI dose reduction and discontinuation of TKI therapy.		37 months
Clinical factors, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.	sex (male, female)	37 months
Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.	age	37 months
Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.	risk group (Sokal, ELTS) at the time of diagnosis	37 months
Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.	duration of previous TKI treatment	37 months
Biological factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.	Duration of molecular response	37 months
Biological factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI.	Molecular response at the time of inclusion in the study	37 months

Collaborators and Investigators

• Sponsor: National Research Center for Hematology, Russia
• Investigators: Principal Investigator: Anna Turkina, Professor, National Research Center for Hematology

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Anticipated): January 15, 2025
• Study Completion (Anticipated): January 15, 2025

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: October 1, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: dasatinib; bosutinib; imatinib; nilotinib; tyrosine kinase inhibitors; chronic myeloid leukimea; the TKI dose reduction; discontinuation treatment TKI
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate; Dasatinib
• Other Study ID Numbers: READIT-2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No