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

Sponsor
National Research Center for Hematology, Russia (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04578847
Collaborator
(none)
100
1
1
60
1.7

Study Details

Study Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Jan 15, 2020
Anticipated Primary Completion Date :
Jan 15, 2025
Anticipated Study Completion Date :
Jan 15, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Overall survival, survival without molecular relapse [37 months]

Secondary Outcome Measures

  1. The proportion of patients with molecular relapse who achieved MMR and DMR after the resumption TKI therapy in standard doses [37 months]

  2. The proportion of patients who resolved the adverse events after TKI dose reduction and discontinuation of TKI therapy [37 months]

  3. The proportion of patients who have TKI withdrawal syndrome after TKI dose reduction and discontinuation of TKI therapy. [37 months]

  4. Clinical factors, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI. [37 months]

    sex (male, female)

  5. Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI. [37 months]

    age

  6. Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI. [37 months]

    risk group (Sokal, ELTS) at the time of diagnosis

  7. Clinical factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI. [37 months]

    duration of previous TKI treatment

  8. Biological factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI. [37 months]

    Duration of molecular response

  9. Biological factor, that affect the preservation of MMR after TKI dose reduction and discontinuation of therapy TKI. [37 months]

    Molecular response at the time of inclusion in the study

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 National Research Center for Hematology Moscow Russian Federation

Sponsors and Collaborators

  • National Research Center for Hematology, Russia

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
National Research Center for Hematology, Russia
ClinicalTrials.gov Identifier:
NCT04578847
Other Study ID Numbers:
  • READIT-2020
First Posted:
Oct 8, 2020
Last Update Posted:
Oct 8, 2020
Last Verified:
Oct 1, 2020
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by National Research Center for Hematology, Russia
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2020