Chronic Lymphocytic Leukemia: Venetoclax-Obinutuzumab Retreatment in Patients with Recurring Disease
- Conditions
- Chronic lymphocytic leukemia (CLL)Therapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 21.1Level: LLTClassification code 10008977Term: Chronic lymphocytic leukemia recurrentSystem Organ Class: 100000004864
- Registration Number
- EUCTR2021-001037-39-BG
- Lead Sponsor
- AbbVie Deutschland GmbH & Co. KG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
•Adult individuals, at least 18 years old.
•Subjects must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
•Adequate marrow function independent of growth factor or transfusion support within 2 weeks of Screening as follows, unless cytopenia is due to marrow involvement of CLL
•Previously completed venetoclax + anti-CD20 antibody ± X (where X is any additional drug) regimen as 1L fixed duration therapy and achieved documented response, defined as CR, CRi, PR, or nPR.
•Patients who will not receive approved second-line therapies as assessed by the investigator and patient preference may be eligible for the study.
•a) For Cohort 1: More than 24 months between the last dose of venetoclax and progression requiring treatment after completion of 1L venetoclax + anti-CD20 antibody ± X treatment; b) for Cohort 2: 12- 24 months between the last dose of venetoclax and progression requiring
treatment after completion of 1L venetoclax + anti-CD20 antibody ± X treatment.
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Pregnancy testing in all females subjects of child-bearing potential; a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at Cycle 1 Day 1 prior to the first dose of study drug; more frequent testing is acceptable if required per local regulation.
•Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control, from Study Day 1 through at least 30 days after the last dose of venetoclax and at least 18 months after the last dose of obinutuzumab. Female subjects of non-childbearing potential do not need to use birth control.
•Male subject who is sexually active with female partner(s) of childbearing potential, must agree, from Study Day 1 for at least 3 months after the last dose of obinutuzumab and/or ve-netoclax, to practice the protocol-specified contraception. In addition, his female partner(s) of childbearing potential must use at least one of the contraceptive measures as defined.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 65
•Subject has not received an intervening treatment for CLL after completing previous treatment with venetoclax + anti-CD20 antibody ± X.
•Subject has no contraindication for all available uric acid reducing agents.
•Subject has not discontinued prior venetoclax + anti-CD20 antibody ± X treatment due to PD during treatment.
•No active or uncontrolled autoimmune hemolytic anemia or immune thrombocytope-nic purpura.
•No history of clinically significant medical conditions or any other reason that the investigator determines would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
•No history of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class.
•No positive test results for, or suspicion of infection (defined as positive hepatitis B surface antibody [HBsAg] serology), based on site standard practices prior to anti-CD20 antibody infusion and obinutuzumab prescribing information.3 Testing should be conducted prior to initiation of obinutuzumab per site standard of care and obinutuzumab prescribing information.
•For subjects who show evidence of hepatitis B infection (HBsAg positive [regardless of anti-body status] or HBsAg negative but anti-HBc positive), consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy.
•Subjects may be included if HBV DNA is undetectable, provided that they are willing to under-go monthly DNA testing, during and for several months following treatment with obinutuzumab. Subjects who have protective titers of hepatitis B surface antibody (HBsAb) af-ter vaccination or prior but cured hepatitis B are eligible.
•No positive test result for hepatitis C (hepatitis C virus [HCV] antibody serology testing), based on site standard practices prior to anti-CD20 antibody infusion and obinutuzumab prescribing information.3
•No known active SARS-CoV-2 infection. If a subject has signs/symptoms suggestive of SARSCoV-2 infection, the subject must have a negative molecular (e.g., PCR) test or 2 negative antigen test results at least 24 hours apart. Note: SARS-CoV-2 diagnostic tests should be
applied following local requirements/recommendations. In addition, if the site considers the subject currently at risk for developing SARS-CoV-2 infection, then the subject should either be tested or advised to come back for study screening after 14 days.
•No conditions that could interfere with drug absorption including but not limited to short bowel syndrome.
•No significant cardiovascular issues, such as uncontrolled or symptomatic arrhythmias, myocardial infarction within 6 months of study treatment, any class III or IV cardiac disease per New York Heart Association.
•No known positive test result(s) for human immunodeficiency virus.
•No significant toxicity from prior treatment that has not resolved to Grade = 1. Exceptions (e.g., alopecia) are allowed per Investigator discretion.
•Subject must not have used known strong cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers from 7 days prior to venetoclax initiation through dose ramp-up, nor other prohibited drugs and food products within 3 days prior to first dose of study drug (see Section 5.3).
•Subject must not have received any live vaccine within 4 weeks prior to the first dose of study drug or be expected need of live vaccination during s
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method