Comparing 4 approaches for leukemia, myeloid, chronic

Inclusion

• +For HQP1351 monotherapy, patients must have CML in any phase (CP, AP, or BP of any phenotype) or Ph+ ALL, with or without T315I mutation
• +For CohortCohortA group of participants sharing a characteristic, followed together.Read more → D, patients with Ph+ BCP ALL or CML LBP must be resistant or intolerant to at least one second or later generation TKI, such as dasatinib, nilotinib, bosutinib and ponatinib, despite optimal supportive care
• +For HQP1351 monotherapy only: Be previously treated with and developed resistance or intolerance to at least two TKIs including ponatinib, imatinib, dasatinib, nilotinib, bosutinib, and asciminib. For patients with a T315I mutation, number of pretreated TKIs is not restricted.
• +The definition of resistance to first-line TKI treatment refers to European Leukemia Net (ELN) recommendations. The definitions are the same for patients in CP, AP, BP, and Ph+ ALL, and apply also to second-line treatment, when first-line treatment was changed for intolerance. The patients must meet at least one criterion:
• +Three months after the initiation of therapy: non-complete hematologic response (CHR) and/or Ph+ \>95%
• +Six months after the initiation of therapy: BCR-ABL1\>10% and/or Ph+ \>35%
• +Twelve months after the initiation of therapy: BCR-ABL1\>1% and/or Ph+ \>0%
• +Then, and at any time after the initiation of therapy: Loss of CHR, or loss of complete cytogenetic response (CCyR), or confirmed loss of major molecular response (MMR) (In 2 consecutive tests, of which one with a BCR-ABL1 transcripts level ≥1%), mutations, clonal chromosome abnormalities in Ph+ cells (CCA/Ph+)
• +The definition of resistance to second-line TKI treatment
• +a) For CML CP patients: the patients must meet at least one criterion as follows:
• +i.) Three months after the initiation of therapy: No CHR or Ph+ \>95% or new mutations
• +ii.) Six months after the initiation of therapy: BCR-ABL1\>10% and/or Ph+ \>65% and/or new mutations
• +iii.) Twelve months after the initiation of therapy: BCR-ABL1\>1% and/or Ph+ \>35% and/or new mutations
• +iv.) Then, and at any time after the initiation of therapy: Loss of CHR or loss of CCyR, new mutations, confirmed loss of MMR (In 2 consecutive tests, of which one with a BCR-ABL1 transcripts level ≥1%), clonal chromosome abnormalities in Ph+ cells (CCA/Ph+)
• +b) For CML AP patients: the patients must meet at least one criterion as follows:
• +i.) Three months after the initiation of therapy: failure to achieve a major hematologic response (MaHR)
• +ii.) At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 4 weeks
• +iii.) At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of a MaHR
• +c) For CML BP and Ph+ ALL patients: the patients must meet at least one criterion as follows:
• +i) One month after the initiation of therapy: failure to achieve a MaHR
• +ii) At any time after the initiation of therapy, the loss of a MaHR, confirmed in at least 2 consecutive analyses separated by at least 1 week
• +iii) At any time after the initiation of therapy, the development of new BCR-ABL kinase domain mutations in the absence of a MaHR
• +Intolerance to TKIs is defined as:
• +Non-hematological AEs: patients with grade 3 or 4 toxicity during TKIs treatment, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments in the absence of a CCyR for CP patients or MaHR for AP/BP or Ph+ ALL patients
• +Hematological AEs: patients with grade 3 or 4 toxicity during TKIs treatment, that is recurrent after unresponsive after optimal management, including dose adjustments in the absence of a CCyR for CP patients or MaHR for AP/BP or Ph+ ALL patients
• +Patients providing written informed consentInformed consentThe process of being told what taking part involves, then choosing freely.Read more → before initiation of any study-related activities
• +Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• +Minimum life expectancy of 3 months or more
• +Patients with adequate organ function as defined below:
• +Creatinine \< 2 × upper limit of normal (ULN); or, creatinine \> 2 × ULN, with 24h glomerular filtration rate (GFR) ≥ 30 mL/min (Cockcroft-Gault)
• +Serum albumin ≥ 3.0 g/dL
• +Total bilirubin \< 1.5 × ULN
• +Aspartate aminotransferase (AST \[Serum glutamic oxaloacetic transaminase (SGOT)\]) and alanine aminotransferase (ALT \[serum glutamate-pyruvate transaminase (SGPT)\]) \< 3 × ULN for institution (\<5×ULN if liver involvement with leukemia)
• +Serum amylase and lipase ≤ 1.5 × ULN
• +Prothrombin time (PT) ≤ 1.5 × ULN
• +Heart function: Left ventricular ejection fraction (LVEF) \> 50%
• +Normal QT interval corrected Fridericia (QTcF) interval on screeningScreeningThe checks done before joining, to see whether a study fits.Read more → electrocardiogram (ECG) evaluation: male ≤450ms, female ≤470ms
• +Ability to comply with study procedures, in the InvestigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →'s opinion
• +For females of childbearing potential, a negative pregnancy test must be established before enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →. And the eligible female and male patients with childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study