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

• Status: Not yet recruiting
• Trial end date: 2027-02-01
• Target enrollment: 0
• Participant gender: All

Summary

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 orally twice daily. Response is determined by PCR (polymerase chain reaction) blood test during the study. Patients who have not achieved a response after 24 months of single agent asciminib will be offered the addition of nilotinib. Nilotinib will be started at 300 mg BID in addition to asciminib if indicated. Patients will discontinue study treatment if they experience disease progression, or unacceptable toxicity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Augusta University
• Collaborator: H. Jean Khoury Cure CML Consortium

Criteria

Inclusion 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-ABL protein. Subtype classification whether b3a2 (e14a2) or b2a2 (e13a2) is not required for study eligibility.

4. Minimal prior CML therapy including a TKI for less than 30 days.

5. ECOG performance status 0-2 (appendix 1)

6. Adequate organ function:

1. AST and ALT < 3 times the institutional upper limit of normal

2. Creatinine < 1.5 times the institutional upper limit of normal

3. Total bilirubin < 1.5 times the institutional upper limit of normal or < 3.0 x the institutional upper limit of normal with Gilbert Syndrome (unless direct bilirubin is within normal limits)

7. 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.)

8. 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.)

Exclusion Criteria:

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. Lipase > institutional upper limit of normal

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. Screening 12-lead ECG showing a baseline corrected QT interval >480msec (patients with a pacemaker will still be eligible with QTc>500msec)