Phase II Study of the Combination of Blinatumomab and Asciminib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Inclusion Criteria:

1. Diagnosis of one of the following: a) Participants ≥18 years of age with previously untreated or minimally pretreatedPh-positive ALL who are not suitable candidates for intensive chemotherapy.Participants who have received no more than one or two courses of chemotherapy withor without other TKIs are considered minimally pretreated and still eligible if theyhave persistently detectable MRD. i. If they are in morphologic remission at enrollment, they are evaluable only MRDresponses, RFS and OS b) Participants ≥ 18 years of age with relapsed/refractoryPh-positive ALL or with previously treated lymphoid blast phase CML

2. Performance status ≤2 (ECOG Scale)

3. Adequate liver function as defined by the following criteria (unless the increasedvalues are judged to be leukemia disease related):

4. Total serum bilirubin ≤ 2 x upper limit of normal (ULN), unless due toGilbert's syndrome

5. Alanine aminotransferase (ALT) ≤ 3 x ULN, OR

6. Aspartate aminotransferase (AST) ≤ 3 x ULN

7. Adequate renal function defined as: a) Creatinine clearance ≥30 mL/min

8. Adequate pancreatic function as defined by the following criteria: a) Serum lipase and amylase < 1.5 x ULN

9. Adequate cardiac function as assessed clinically by history and physicalexamination.

10. For females of childbearing potential, a negative urine pregnancy test must bedocumented

11. Willingness to use adequate contraception prior to study entry, for the duration ofstudy participation, and for 4 months after completion of study participation. Forwomen of child-bearing potential, adequate methods of contraception include:complete abstinence, hormonal contraception (i.e. birth control pills, injection,implant, transdermal patch, vaginal ring), intrauterine device (IUD), tubal Ligationor hysterectomy, subject/partner post vasectomy, implantable or injectablecontraceptives, and condoms plus spermicide

12. Ability to understand and the willingness to sign a written informed consentdocument.

13. Signed informed consent

Exclusion Criteria:

1. Active serious infection not controlled by oral or intravenous antibiotics.

2. Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma orsquamous cell carcinoma) that in the investigator's opinion will shorten survival toless than 1 year.

3. Active Grade III-V cardiac failure as defined by the New York Heart AssociationCriteria.

4. Prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) unless correctedafter electrolyte replacement or approved by cardiologist

5. History or presence of clinically relevant CNS pathology such as epilepsy, childhoodor adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia,Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. (Participants with active CNS leukemia will NOT be excluded)

6. Treatment with any investigational antileukemic agents or chemotherapy agents in thelast 7 days before study entry, unless full recovery from side effects has occurredor patient has rapidly progressive disease judged to be life-threatening by theinvestigator. Cytarabine 2 g/m2 (or alternative) for cytoreduction is permitted.

7. Pregnant and lactating women will not be eligible; women of childbearing potentialshould have a negative pregnancy test prior to entering on the study and be willingto practice methods of contraception. Women do not have childbearing potential ifthey have had a hysterectomy or are postmenopausal without menses for 12 months. Inaddition, men enrolled on this study should understand the risks to any sexualpartner of childbearing potential and should practice an effective method of birthcontrol.