RECRUITING

Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

Conditions

Chronic Myeloid Leukemia, Chronic Phase Adult CML Leukemia, Myeloid Leukemia,Myeloid, Chronic Chronic Myeloid Leukemia tyrosine kinase inhibitors H. Jean Khoury Cure CML Consortium HJKC3-0004

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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 study is a multicenter Phase 2, non-randomized, open-label single-group frontline study administering asciminib in patients with newly diagnosed Chronic Myeloid Leukemia-Chronic Phase (CML-CP). The aim of this study is to evaluate the efficacy and safety of asciminib in newly diagnosed CML-CP. Patients will receive asciminib 80 mg orally once daily during the single asciminib phase. Response is determined by PCR (polymerase chain reaction) blood test during the study. Patients who have not achieved a response after 24 months (but no later than 36 months) of single agent asciminib will be offered the addition of a low dose tyrosine kinase inhibitor (low-TKI) namely dasatinib, imatinib, or nilotinib at the investigator's discretion. The following doses of the TKIs will be used: 1. Dasatinib 50 mg daily 2. Imatinib 300 mg daily 3. Nilotinib 300 mg daily Patients will discontinue study treatment if they experience disease progression, or unacceptable toxicity.

Official Title

Asciminib as Initial Therapy With Addition of Lower Dose Tyrosine Kinase Inhibitors for Patients With Chronic Myeloid Leukemia Who do Not Achieve a Deep Molecular Remission (ALERT CML)

Quick Facts

Study Start:2022-04-22

Study Completion:2027-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05143840

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 old 2. Willing and able to give informed consent 3. Newly diagnosed with CML in chronic phase within 6 months from confirmed diagnosis and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR::ABL1 protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility. 4. Minimal prior CML therapy with a TKI for less than or equal to 30 days. Treatment with hydroxyurea, busulfan, anagrelide or other non-specific chemotherapy agents is allowed with no time restrictions within the eligible time from diagnosis. 5. ECOG performance status 0-2 (appendix 1) 6. Adequate organ function: 1. AST and ALT \< 3 times the institutional upper limit of normal (ULN) 2. Creatinine \< 1.5 times the institutional upper limit of normal 3. Total bilirubin \< 1.5 times the institutional ULN or \< 3.0 x the institutional ULN with Gilbert Syndrome (unless direct bilirubin is within normal limits) 7. Adequately controlled blood pressure, defined as systolic blood pressure of \<140 mmHq and diastolic of \<90 mmHg, at the time of enrollment. 8. Serum lipase less than or equal to 1.5 x ULN. For serum lipase \> ULN - less than or equal to 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis. 9. Female patients must meet one of the following: 1. Postmenopausal for at least one year before the screening visit, 2. Surgically sterile 3. If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug, 4. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable 5. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.) 10. Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following: 1. Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose 2. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable 3. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)	1. Patients with accelerated or blast phase CML (refer to appendix 4) 2. Active second malignancy requiring active treatment 3. History of recent (within 12 months) acute pancreatitis or chronic pancreatitis 4. Subjects who have previously received treatment with asciminib. 5. Subjects with PLT count \< 50,000 mm3 or ANC of \< 500 mm3 or Hemoglobin \< 8 g/dL 6. Cardiac or cardiac repolarization abnormality, including any of the following: 1. History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG) 2. 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) 3. QTcF at screening greater than or equal to 450 msec (male patients), greater than or equal to 460 msec (female patients) unless patient has a pacemaker 4. Long QT syndrome, family history of idiopathic sudden death or congenital long 7. Pregnant or lactating 8. Taking a strong inhibitors or inducers of CYP3A4 or CYP3A4 substrates with narrow therapeutic index (refer to appendix 6) at time of enrollment 9. Unable to comply with lab appointment schedule and PRO assessments 10. Another investigational drug within 4 weeks of enrollment 11. Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol 12. Patient has undergone a prior allogeneic stem cell transplant 13. Known clinical history of active HBV infection

Inclusion Criteria

Exclusion Criteria

1. Age ≥18 years old
2. Willing and able to give informed consent
3. Newly diagnosed with CML in chronic phase within 6 months from confirmed diagnosis and have either the b3a2 (e14a2) or b2a2 (e13a2) variants that give rise to the p210 BCR::ABL1 protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility.
4. Minimal prior CML therapy with a TKI for less than or equal to 30 days. Treatment with hydroxyurea, busulfan, anagrelide or other non-specific chemotherapy agents is allowed with no time restrictions within the eligible time from diagnosis.
5. ECOG performance status 0-2 (appendix 1)
6. Adequate organ function:
1. AST and ALT \< 3 times the institutional upper limit of normal (ULN)
2. Creatinine \< 1.5 times the institutional upper limit of normal
3. Total bilirubin \< 1.5 times the institutional ULN or \< 3.0 x the institutional ULN with Gilbert Syndrome (unless direct bilirubin is within normal limits)
7. Adequately controlled blood pressure, defined as systolic blood pressure of \<140 mmHq and diastolic of \<90 mmHg, at the time of enrollment.
8. Serum lipase less than or equal to 1.5 x ULN. For serum lipase \> ULN - less than or equal to 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis.
9. Female patients must meet one of the following:
1. Postmenopausal for at least one year before the screening visit,
2. Surgically sterile
3. If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug,
4. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable
5. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable contraception methods.)
10. Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
1. Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose
2. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable
3. Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)

1. Patients with accelerated or blast phase CML (refer to appendix 4)
2. Active second malignancy requiring active treatment
3. History of recent (within 12 months) acute pancreatitis or chronic pancreatitis
4. Subjects who have previously received treatment with asciminib.
5. Subjects with PLT count \< 50,000 mm3 or ANC of \< 500 mm3 or Hemoglobin \< 8 g/dL
6. Cardiac or cardiac repolarization abnormality, including any of the following:
1. History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
2. 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)
3. QTcF at screening greater than or equal to 450 msec (male patients), greater than or equal to 460 msec (female patients) unless patient has a pacemaker
4. Long QT syndrome, family history of idiopathic sudden death or congenital long
7. Pregnant or lactating
8. Taking a strong inhibitors or inducers of CYP3A4 or CYP3A4 substrates with narrow therapeutic index (refer to appendix 6) at time of enrollment
9. Unable to comply with lab appointment schedule and PRO assessments
10. Another investigational drug within 4 weeks of enrollment
11. Any serious medical or psychiatric illness that could, in the investigator's opinion, interfere with the completion of treatment according to this protocol
12. Patient has undergone a prior allogeneic stem cell transplant
13. Known clinical history of active HBV infection

Contacts and Locations

Study Contact

Kelly Jenkins, MSN, RN

CONTACT

706-721-1206

kejenkins@augusta.edu

GCC Clinical Trials Office

CONTACT

706-721-2505

Cancer_Center_Trials@augusta.edu

Principal Investigator

Jorge Cortes, MD

PRINCIPAL_INVESTIGATOR

Augusta University

Study Locations (Sites)

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Huntsman Cancer Institute

Salt Lake City, Utah, 84112

United States

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Augusta University

Jorge Cortes, MD, PRINCIPAL_INVESTIGATOR, Augusta University

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 Date2022-04-22

Study Completion Date2027-02

Study Record Updates

Study Start Date2022-04-22

Study Completion Date2027-02

Terms related to this study

Keywords Provided by Researchers

Chronic Myeloid Leukemia
Adult CML
tyrosine kinase inhibitors
H. Jean Khoury Cure CML Consortium
HJKC3-0004

Additional Relevant MeSH Terms

Chronic Myeloid Leukemia, Chronic Phase
Adult CML
Leukemia, Myeloid
Leukemia,Myeloid, Chronic