• Participants must meet the following criteria on screening examination to be eligible to participate in the study:

‣ Participants must have cytopathologically confirmed CD19+ BCR-ABL1+ acute leukemia (B-cell ALL, mixed phenotype acute leukemia, or CML in lymphoid blast crisis with ≥ 5% lymphoblasts.)22

• BCR-ABL1 positive status may be confirmed by FISH, karyotype analysis, or molecular testing for p210 (b2a2 or b3a2) or p190 (e1a2) transcripts.

∙ Patients with asymptomatic central nervous system (CNS) disease are eligible and may be treated concurrently with intrathecal chemotherapy.

⁃ Dose escalation: Participants must NOT be suitable for or willing to receive standard intensive induction chemotherapy.

⁃ Dose expansion: Participants aged 18 years and older will be eligible regardless of suitability for intensive induction chemotherapy.

⁃ The following groups are not considered suitable for standard intensive induction chemotherapy:

• Participants who have not received standard intensive induction chemotherapy and are aged ≥ 50 years.

• Participants who have not received standard intensive induction chemotherapy and are aged 18 to 49 years and unfit due to co-morbidity or other factors to receive intensive chemotherapy. Specific criteria that would suggest that a patient is unsuitable for intensive induction chemotherapy include:

‣ Severe cardiac comorbidity (congestive heart failure or documented cardiomyopathy with EF ≤50%).

⁃ Severe pulmonary comorbidity (documented pulmonary disease with DLCO ≤ 65% or FEV1 ≤ 65%, or dyspnea at rest, or requiring oxygen).

⁃ ECOG performance status of 2 due to medical conditions unrelated to leukemia.

⁃ Any other comorbidity that the physician judges to be incompatible with intensive cytotoxic chemotherapy.

• Participants aged ≥ 18 years with disease that is relapsed or refractory to 1 or more cycles of standard intensive induction chemotherapy.

‣ ECOG performance status 0-3 (Appendix A). ECOG value of 3 is allowed after documented discussion with PI, if poor performance status is attributed to underlying disease.

⁃ Participants must have normal organ function as defined below:

• Creatinine ≤ 1.5x institutional upper limit of normal.

• Amylase and lipase values ≤ 3.0x institutional upper limit of normal.

• Alkaline phosphatase ≤ 2.5x institutional upper limit of normal (unless considered to be not of hepatic origin) (any level permitted), and/or unless felt to be clearly related to disease where ≤ 5x institutional upper limit of normal is permitted, after discussion with the overall PI.

• AST(SGOT)/ALT(SGPT) ≤ 3x institutional upper limit of normal unless felt to be clearly related to disease where ≤ 5x institutional upper limit of normal is permitted, after discussion with the overall PI.

• Total bilirubin - ≤1.5x institutional upper limit of normal (≤ 3x upper limit of normal in patients with known or suspected Gilbert's syndrome).

⁃ The effects of ASCIMINIB on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

• Women of child-bearing potential must agree to use highly effective methods of contraception during dosing and for 30 days after study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

• Allowable methods of birth control:

‣ Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.

⁃ Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.

⁃ Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.

⁃ Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception.

• Sexually active males must use a condom during intercourse while taking the drug and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. -- Ability to understand and the willingness to sign a written informed consent document and comply with all study procedures.