RECRUITING

Phase II Study of Asciminib for Second-line Treatment of Chronic Phase Chronic Myeloid Leukemia

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open label, phase 2 study investigating asciminib in patients previously treated with one line of TKI therapy.

Official Title

Phase II Study of Asciminib for Second-line Treatment of Chronic Phase Chronic Myeloid Leukemia

Quick Facts

Study Start:2025-02-14

Study Completion:2028-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06629584

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age ≥ 18 years. 2. Diagnosis of Ph-positive (by cytogenetics or FISH) or BCR-ABL-positive (by PCR) CML in chronic phase and have received one prior line of therapy with a TKI. 3. History of treatment failure defined as either: * BCR::ABL1 \>0.1% for patients with intolerance to first-line TKI * Less than complete hematologic response (CHR) at ≥3 months * No partial cytogenetic response at ≥3 months * BCR::ABL1 ≥ 10% at if 3-6 months * BCR::ABL1 ≥ 1% at ≥6 months * Loss of CCyR or development of mutations or other clonal chromosomal abnormalities at any time during TKI treatment 4. ECOG performance status ≤ 2. 5. Adequate end organ function within 12 days before the first dose of asciminib treatment. Patients with mild to moderate renal and hepatic impairment are eligible if: * Total bilirubin ≤ 3.0 x ULN without AST/ALT increase * Aspartate transaminase (AST) ≤ 5.0 x ULN * Alanine transaminase (ALT) ≤ 5.0 x ULN * Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN and ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis * Alkaline phosphatase ≤ 2.5 x ULN * Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft-Gault formula 6. 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 the start of 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.	1. Patients with a history of T315I mutation. 2. Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \< 40% by echocardiogram or multi-gated acquisition (MUGA) scan. 3. Patients with a history of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block). 4. Corrected QT interval (QTc) of \> 450 milliseconds (ms) on baseline electrocardiogram (ECG or EKG) (using the Fridericia Formula) 5. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. * Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication. 6. Patients with known active infection with human immunodeficiency virus (HIV) or Hepatitis B or C. 7. Patients with known conditions that would significantly affect the ingestion or gastrointestinal absorption of drugs administered orally. 8. Nursing women, women of childbearing potential (WOCBP) with positive blood or urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (see inclusion criteria 8) 9. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis. 10. ANC \< 500/mm3, platelet count \< 50,000 mm3. 11. History of other active malignancy within 2 years prior to study entry except for previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively. 12. Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study.

Inclusion Criteria

Exclusion Criteria

1. Age ≥ 18 years.
2. Diagnosis of Ph-positive (by cytogenetics or FISH) or BCR-ABL-positive (by PCR) CML in chronic phase and have received one prior line of therapy with a TKI.
3. History of treatment failure defined as either:
* BCR::ABL1 \>0.1% for patients with intolerance to first-line TKI
* Less than complete hematologic response (CHR) at ≥3 months
* No partial cytogenetic response at ≥3 months
* BCR::ABL1 ≥ 10% at if 3-6 months
* BCR::ABL1 ≥ 1% at ≥6 months
* Loss of CCyR or development of mutations or other clonal chromosomal abnormalities at any time during TKI treatment
4. ECOG performance status ≤ 2.
5. Adequate end organ function within 12 days before the first dose of asciminib treatment. Patients with mild to moderate renal and hepatic impairment are eligible if:
* Total bilirubin ≤ 3.0 x ULN without AST/ALT increase
* Aspartate transaminase (AST) ≤ 5.0 x ULN
* Alanine transaminase (ALT) ≤ 5.0 x ULN
* Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN and ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis
* Alkaline phosphatase ≤ 2.5 x ULN
* Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft-Gault formula
6. 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 the start of 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.

1. Patients with a history of T315I mutation.
2. Patients with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \< 40% by echocardiogram or multi-gated acquisition (MUGA) scan.
3. Patients with a history of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block).
4. Corrected QT interval (QTc) of \> 450 milliseconds (ms) on baseline electrocardiogram (ECG or EKG) (using the Fridericia Formula)
5. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
* Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
* Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
6. Patients with known active infection with human immunodeficiency virus (HIV) or Hepatitis B or C.
7. Patients with known conditions that would significantly affect the ingestion or gastrointestinal absorption of drugs administered orally.
8. Nursing women, women of childbearing potential (WOCBP) with positive blood or urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception (see inclusion criteria 8)
9. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
10. ANC \< 500/mm3, platelet count \< 50,000 mm3.
11. History of other active malignancy within 2 years prior to study entry except for previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively.
12. Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study.

Contacts and Locations

Study Contact

Ghayas Issa, MD

CONTACT

(713) 745-6798

gcissa@mdanderson.org

Principal Investigator

Ghayas Issa, MD

PRINCIPAL_INVESTIGATOR

The University of Texas MD Anderson Cancer Center

Study Locations (Sites)

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Ghayas Issa, MD, PRINCIPAL_INVESTIGATOR, The University of Texas MD Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-14

Study Completion Date2028-12-31

Study Record Updates

Study Start Date2025-02-14

Study Completion Date2028-12-31

Terms related to this study

Additional Relevant MeSH Terms

Malignant Solid Tumors