Venetoclax After TKI to Target Persisting Stem Cells in CML

NCT05701215 | Active Not Recruiting Phase 2

• 2 other identifiers: VARIANT2022-003069-39
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Chronic Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• stem cell change

  Reduction of BCR::ABL1 stem cells measured by quantitative genomic PCR in bone marrow after venetoclax administration.

  at 6 months and 12 months after start of Venetoclax

Secondary Outcomes (3)

• European Organisation for Research and Treatment of Cancer - Quality of Life C30 - Questionnaire

  at 6 months and 12 months after start of Venetoclax

• Kinetics of BCR::ABL1-transcript expression

  monthly after start of Venetoclax until month 12

• Overall survival (OS)

  monthly after start of Venetoclax until month 12

Study Arms (1)

Venetoclax

EXPERIMENTAL

Venetoclax will be taken orally once daily (400 mg) for 12 months after stop of TKI

Drug: Venetoclax

Interventions

Venetoclax DRUG

Venetoclax will be taken orally once daily (400 mg) for 12 months

Venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with diagnosis of chronic phase CML with cytogenetic confirmation of the Philadelphia (Ph) chromosome
• Ph negative cases or patients with variant translocations who are BCR::ABL1 positive in multiplex PCR are also eligible
• Typical b2a2 and/or b3a2 BCR::ABL1 transcripts
• Subject must be ≥ 18 years of age
• Stored DNA from initial diagnosis (prior TKI treatment) for BCR::ABL1 breakpoint analysis
• 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
• At least 3 years of TKI therapy
• Patients who failed to discontinue TKI in a prior discontinuation attempt are still eligible if they fulfill criteria 6 after retreatment with TKI
• WHO performance status 0-2
• 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.
• 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),

You may not qualify if:

• Concomitant use of strong CYP3A-Inhibtors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) is contraindicated
• Concomitant use of moderate CYP3A-Inhibitors (e.g., ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) should be avoided.
• Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax as they contain inhibitors of CYP3A
• Concomitant use of venetoclax with P-gp and BCRP inhibitors
• 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
• Concomitant use of preparations containing St. John´s wort
• Patients with severe renal impairment (Crea-Clearance \< 30 ml/min) or on dialysis
• Patients with severe hepatic impairment
• 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
• Known impaired cardiac function
• Impaired gastrointestinal function or disease that may alter the absorption of study drug
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
• Active or uncontrolled infections at the time of enrolment
• Known HIV sero-positivity or known active hepatitis B or C infection (HIV testing is not required)
• Participation in another clinical study with other investigational drugs within 14 days prior to enrolment

Sponsors & Collaborators

• Thomas Ernst, PD Dr. med.: lead
• Ludwig-Maximilians - University of Munich: collaborator
• AbbVie: collaborator

Study Sites (2)

Uniklinik der RWTH Aachen

Aachen, 52074, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas Ernst, Prof. Dr.

  University Hospital Jena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: January 27, 2023
• Study Start: August 31, 2023
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)