Phase II Study Assessing the Efficacy and Toxicity of Olverembatinib Monotherapy in Patients With Chronic Myeloid Leukemia in Chronic Phase After Failing One Prior Therapy With a Second Generation Tyrosine Kinase Inhibitor or Asciminib

Eligibility Criteria:

Adult participants age ≥18 years.

Participants must have a diagnosis of Ph-positive or BCR::ABL1 positive CML in early chronic phase.

Participants who received prior hydroxyurea, 1 to 2 doses of cytarabine, and/or an FDA approved TKI for ≤ 30 days are eligible.

Participants with additional chromosomal abnormalities at diagnosis (early disease) and no other criteria for accelerated phase will be eligible for this study.

ECOG performance status ≤ 2.

Participants must have adequate end organ function, defined as the following: total bilirubin ≤1.5x ULN (unless secondary to Gilbert's disease, in which case should be ≤ 2.5x ULN), SGPT or SGOT ≤ 3x ULN, creatinine clearance ≥ 30mL/min calculated using modified Cockcroft-Gault.

Ability to understand and the willingness to sign a written informed consent document.

The effects of olverembatinib 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, for the duration of study participation, and 4 months after completion of olverembatinib administration. This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participants presents with an applicable exclusionary factor which may be one of the following:

* Postmenopausal (no menses in greater than or equal to 12 consecutive months).

* History of hysterectomy or bilateral salpingo-oophorectomy.

* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

* History of bilateral tubal ligation or another surgical sterilization procedure.

Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Participant post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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.

* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of olverembatinib administration.

* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured.

Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2 or better.

* Early chronic phase: time from diagnosis to therapy ≤ 12 months.

* Late chronic phase: time from diagnosis to therapy \> 12 months.

* Blastic phase: presence of 30% blasts or more in the peripheral blood or bone marrow.

* Accelerated phase CML: presence of any of the following features:

i. Peripheral or marrow blasts 15% or more. ii. Peripheral or marrow basophils 20% or more. iii. Thrombocytopenia \< 100 x 109/L unrelated to therapy. iv. Documented extramedullary blastic disease outside liver or spleen.

Phase II Study Assessing the Efficacy and Toxicity of Olverembatinib Monotherapy in Patients With Chronic Myeloid Leukemia in Chronic Phase After Failing One Prior Therapy With a Second Generation Tyrosine Kinase Inhibitor or Asciminib

What this study is about

Phase II Study Assessing the Efficacy and Toxicity of Olverembatinib Monotherapy in Patients With Chronic Myeloid Leukemia in Chronic Phase After Failing One Prior Therapy With a Second Generation Tyrosine Kinase Inhibitor or Asciminib

What this study is about