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临床试验/NCT05701215
NCT05701215已完成2 期

Venetoclax After TKI to Target Persisting Stem Cells in CML

Thomas Ernst, PD Dr. med.4 个研究点 分布在 1 个国家目标入组 10 人开始时间: 2023年8月31日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
已完成
发起方
入组人数
10
试验地点
4
主要终点
stem cell change
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型
Interventional
分配方式
Na
干预模型
Single Group
主要目的
Treatment
盲法
None

入排标准

年龄范围
18 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •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),
  • •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.
  • •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.
  • •Negative pregnancy test in women of childbearing potential
  • •Subject must voluntarily sign and date an informed consent

排除标准

  • •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
  • •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
  • •Subject has acute leukemia
  • •Subject has known active CNS involvement.
  • •Hypersensitivity to venetoclax or any component of the formulation

研究组 & 干预措施

Venetoclax

Experimental

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

干预措施: Venetoclax (Drug)

结局指标

主要结局

stem cell change

时间窗: at 6 months and 12 months after start of Venetoclax

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

次要结局

  • 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)

研究者

发起方
Thomas Ernst, PD Dr. med.
申办方类型
Other
责任方
Sponsor Investigator
主要研究者

Thomas Ernst, PD Dr. med.

Principal Investigator

University of Jena

研究点 (4)

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