Evaluation of a treatment with bendamustine, followed by obinutuzumab, zanubrutinib and venetoclax in patients with relapsed chronic lymphocytic leukemia
- Conditions
- Relapsed/refractory chronic lymphocytic leukemiaMedDRA version: 21.1Level: PTClassification code: 10008958Term: Chronic lymphocytic leukaemia Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-502201-16-00
- Lead Sponsor
- niversity Of Cologne
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 42
Relapsed/refractory CLL in need of treatment according to iwCLL criteria. In case of a recent previous treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods before start of the study treatment in the CLL2-BZAG trial: - chemotherapy = 28 days / - antibody treatment = 14 days/ -kinase inhibitors, BCL2-antagonists or immuno-modulatory agents = 3 days /- corticosteroids may be applied until the start of the BZAG-regimen, these have to be reduced to an equivalent of = 20mg prednisolone per day during treatment. Please note: Patients with a progression during previous treatment with venetoclax, ibrutinib or another BTK inhibitor, as well as patients with a known resistance mutation (e.g. BTK-/PLCg2) are excluded from study participation. However, patients who progressed after termination of treatment with venetoclax, ibrutinib, other BTK inhibitors and/or obinutuzumab or who stopped treatment due to intolerance to ibrutinib are eligible for participation., Adequate renal function, as indicated by a creatinine clearance =30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24 hr. urine collection, Adequate hematologic function as indicated by a neutro-phil count = 1.0 x 109/L, a hemoglobin value =8.0 g/dL and a platelet count = 25 x 109/L, unless directly attributable to the patient´s CLL (e.g. bone marrow infiltration), in this case, platelet count should be = 10 × 109/L, Adequate liver function as indicated by a total bilirubin =2x, AST/ALT =2.5x the institutional ULN value, unless di-rectly attributable to the patient’s CLL or to Gilbert’s Syn-drome, Negative serological testing for hepatitis B (HBsAg nega-tive and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every 4 weeks until one year after last dosage of GA101 (obinutuzumab) or until the last dose of zanubrutinib, whichever occurs later), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration, Age = 18 years, ECOG 0 to 2, ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms), Life expectancy = 6 months, Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements
(Suspicion of) transformation of CLL (i.e. Richter’s transformation, pro-lymphocytic leukemia) or central nervous system (CNS) involvement, Known hypersensitivity to obinutuzumab (GA101), ve-netoclax (ABT-199), zanubrutinib (BGB-3111) or any of the excipients Please note: Patients with a known hypersensitivity to bendamustine are allowed to participate but will not receive a debulking with bendamustine, Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment), Fertile men or women of childbearing potential unless: -surgically sterile or = 2 years after the onset of menopause, or -willing to use two methods of reliable contraception including one highly effective (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after end of study treatment., Vaccination with a live vaccine = 28 days prior to registra-tion, Legal incapacity, Prisoners or subjects who are institutionalized by regulatory or court order, Persons who are in dependence to the sponsor or an in-vestigator, Progression during previous treatment with venetoclax, ibrutinib or another BTK inhibitor, and/or presence of known mutations associated with resistance to therapy, e.g. Bruton´s Tyrosine Kinase and Phospholipase C Gamma 2 (PLCg2), Confirmed progressive multifocal leukoencephalopathy (PML), Malignancies other than CLL currently requiring systemic therapies, Uncontrolled infection requiring systemic treatment, Any comorbidity or organ system impairment rated with a CIRS (cumulative illness rating scale) score of 4, excluding the eyes/ears/nose/throat/larynx organ system or any other life-threatening illness, medical condition or organ system dysfunction that – in the investigator´s opinion - could compromise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastroin-testinal tract), Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diathe-sis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure = 4 weeks or stroke/intracranial hem-orrhage = 6 months., Requirement of therapy with strong CYP3A4 inhibitors/inducers or anticoagulant with phenprocoumon (marcumar) or other vitamin K-antagonists, Use of investigational agents = 28 days prior to start of study treatment, however, kinase inhibitors, BCL2-antagonists and antibody treatment are allowed in ac-cordance with inclusion criterion number 1 (see above).
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