chronic myeloid leukemia in chronic phase chronic myeloid leukemia
Conditions
Interventions
Single-arm study in patients with CML-CP who have failed to attain a successful treatment-free remission after TKI discontinuation (defined as loss of MMR or DMR) and regained a DMR (defined as MR4.5
Sponsors
Kiyoi Hitoshi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Major BCR-ABL1 positive CML-CP 2) Aged 18 years or older 3) Less than or equal to 2 of performance status by ECOG 4) Patients who have failed to attain a successful treatment-free remission after TKI discontinuation in a formal clinical study or in clinical practice (the latter case includes only those who fulfilled conditions both TKI therapy over 3 years and MR4.5 over 2 years) 5) Patients who achieved MR4.5 after retreatment with TKI other than ponatinib 6) Patients who can visit the hospital on scheduled days 7) With written informed consent for the clinical trial (the protector's signature is required in those aged less than 20 years old)
Exclusion criteria
Exclusion criteria: 1) Prior history of accelerated or blastic phase 2) Prior history of hematopoietic stem cell transplantation 3) With following organ dysfunction (1) T-Bil >3 x ULN (excluding Gilbert syndrome) (2) AST or ALT >5 x ULN (3) Cr >3 x ULN or eGFR 2 x ULN (5) Heart failure within 6 months (6) Transient ischemic attack within 6 months (7) Acute pancreatitis within 1 year (8) Uncontrolled or life-threatening arrhythmia (9) QTc >470 ms on ECG 4) Poor adherence to TKI 5) Pregnant women or women who are expected to be pregnant during this study 6) With hepatitis B virus infection (positive for HBs-Ag or HBV-DNA PCR) 7) Major surgery within 28 days before study registration 8) With a diagnosis of alcohol dependence 9) With uncontrolled or active malignant disease 10) Prior history of the vascular event (regardless of arterial or venous disease) 11) With the following risk factor for thrombosis (regardless of medication) (1) Uncontrolled hypertension (dBP >90 mm Hg or sBP >140 mm Hg) (2) Uncontrolled dyslipidemia (TG >450 mg/dL or LDL >160 mg/dL) (3) Uncontrolled diabetes mellitus (HbA1c >7.0%) (4) Ankle-brachial pressure index of less than 0.90 or more than 1.40 12) With any reason considered to render the patient inadequate for the protocol therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MMR rate at 12 months of ponatinib discontinuation | — |
Secondary
| Measure | Time frame |
|---|---|
| MMR/MR4.5 rate at 24 months of ponatinib discontinuation MR4.5 rate at 12 months of ponatinib discontinuation Completion rate and the adverse events of ponatinib maintenance therapy for 12 months Adverse events during retreatment with ponatinib Cumulative MMR rate by 6 months in patients who started retreatment with TKI Correlation between ponatinib pharmacologic concentration and treatment-free remission rate Correlation between T/NK cell profiling (regulatory T cells, CD4/CD8 ratio, and effector T cells, etc.) and treatment-free remission rate Correlation between serum proteome profiling (mainly cytokines) and treatment-free remission rate Correlations between risk stratification at diagnosis of CML (Sokal or EUTOS score), TKI treatment duration, MMR/DMR duration, or the depth of molecular response and treatment-free remission rate Correlation between peripheral endothelial cell profiling and adverse events during ponatinib therapy Correlation between patients' backgrounds and adverse events | — |
Contacts
Public ContactNoriyoshi Iriyama
30-1 Oyaguchi Kamicho Itabashi-ku, Tokyo
Outcome results
None listed