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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.
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The TKI dose reduction | Experimental | Imatinib, nilotinib, dasatinib or bosutinib; the two stage of TKI dose reduction phase for 12 months (6 months and 6 months, respectively). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Imatinib | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival, survival without molecular relapse | 37 months |
| 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 |
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Inclusion Criteria:
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anna Turkina, Professor | National Research Center for Hematology | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Research Center for Hematology | Moscow | Russia |
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| Nilotinib | 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 | 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 | 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. |
|
| 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 |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000068877 | Imatinib Mesylate |
| C498826 | nilotinib |
| D000069439 | Dasatinib |
| C471992 | bosutinib |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |
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