Venetoclax After TKI to Target Persisting Stem Cells in CML

Trial Title: Venetoclax After TKI to Target Persisting Stem Cells in CML

NCT ID: NCT05701215

Condition: Chronic Myeloid Leukemia

Conditions: Official terms:
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Venetoclax

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Venetoclax
Description: Venetoclax will be taken orally once daily (400 mg) for 12 months
Arm group label: Venetoclax

Summary: There is currently no available treatment, capable to increase the rate of sustained deep molecular remissions after TKI discontinuation in CML. Venetoclax could be such a drug. The study will provide unprecedented biological insights on the effects of venetoclax in controlling minimal residual stem cell disease induced by long-term prior TKI therapy. If the study would be positive, the findings could become practice changing for patients in deep molecular remission under TKI and willing to tolerate a temporary additional treatment.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Patients with diagnosis of chronic phase CML with cytogenetic confirmation of the Philadelphia (Ph) chromosome 2. Ph negative cases or patients with variant translocations who are BCR::ABL1 positive in multiplex PCR are also eligible 3. Typical b2a2 and/or b3a2 BCR::ABL1 transcripts 4. Subject must be ≥ 18 years of age 5. Stored DNA from initial diagnosis (prior TKI treatment) for BCR::ABL1 breakpoint analysis 6. BCR::ABL1 transcript level according to the international scale (IS) of MR4 or better which has been confirmed three times within the past 13 months and was assessed by an IS-certified reference laboratory, such as of the University Jena or another MR4-certified laboratory in Germany 7. At least 3 years of TKI therapy 8. Patients who failed to discontinue TKI in a prior discontinuation attempt are still eligible if they fulfill criteria 6 after retreatment with TKI 9. WHO performance status 0-2 10. Adequate end organ function as defined by: - Total bilirubin (TBL) < 3 x Upper Limit of Normal (ULN); patients with Gilbert's syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN, - Creatinine Clearance (CrCl) ≥ 30 millilitres per minute (mL/min) as calculated using Cockcroft-Gault formula, Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis. 11. Patients must have the following laboratory values within normal limits or corrected to within normal limits with supplements: - Potassium (potassium increase of up to 6.0 mmol/L is acceptable if associated with CrCl ≥ 90 mL/min), - Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with CrCl ≥ 90 mL/min), - Magnesium (magnesium increase of up to 3.0 mg/dL or 1.23 mmol/L if associated with CrCl ≥ 90 mL/min), - For patients with mild to moderate renal impairment (CrCl ≥ 30 mL/min and <90 mL/min) - potassium, total calcium (corrected for serum albumin) and magnesium should be within normal limits or corrected to within normal limits with supplements. 12. Women of childbearing age must use a highly effective method of contraception while using venetoclax. Women using hormonal contraceptives should also use a barrier method. 13. Negative pregnancy test in women of childbearing potential 14. Subject must voluntarily sign and date an informed consent Exclusion Criteria: 1. Concomitant use of strong CYP3A-Inhibtors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) is contraindicated 2. Concomitant use of moderate CYP3A-Inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided. 3. Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax as they contain inhibitors of CYP3A 4. Concomitant use of venetoclax with P-gp and BCRP inhibitors 5. Concomitant use of venetoclax with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided 6. Concomitant use of preparations containing St. John´s wort 7. Patients with severe renal impairment (Crea-Clearance < 30 ml/min) or on dialysis 8. Patients with severe hepatic impairment 9. Patients who are pregnant or breast feeding, or females of reproductive potential not employing an effective method of birth control. Female patients must agree to employ an effective barrier method of birth control throughout the study and for and for at least 30 days after ending venetoclax treatment 10. Known impaired cardiac function 11. Impaired gastrointestinal function or disease that may alter the absorption of study drug 12. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy 13. Active or uncontrolled infections at the time of enrolment 14. Known HIV sero-positivity or known active hepatitis B or C infection (HIV testing is not required) 15. Participation in another clinical study with other investigational drugs within 14 days prior to enrolment 16. Any medical, mental, psychological or psychiatric condition that in the opinion of the investigator would not permit the patient to complete the study or understand the patient information 17. Subject has acute leukemia 18. Subject has known active CNS involvement. 19. Hypersensitivity to venetoclax or any component of the formulation

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Uniklinik der RWTH Aachen

Address:
City: Aachen
Zip: 52074
Country: Germany

Status: Recruiting

Contact:
Last name: Martina Crysandt, Dr. med.
Email: mcrysandt@ukaachen.de

Facility:
Name: Universitätsklinikum Jena

Address:
City: Jena
Zip: 07747
Country: Germany

Status: Recruiting

Contact:
Last name: Thomas Ernst, Prof. Dr.

Phone: +49 3641

Phone ext: 9324201
Email: thomas.ernst@med.uni-jena.de

Start date: August 31, 2023

Completion date: December 1, 2025

Lead sponsor:
Agency: Thomas Ernst, PD Dr. med.
Agency class: Other

Collaborator:
Agency: Ludwig-Maximilians - University of Munich
Agency class: Other

Collaborator:
Agency: AbbVie
Agency class: Industry

Source: University of Jena

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05701215