A prospective, open-label, multicenter phase-II-trial to evaluate the efficacy and safety of a sequential regimen of Bendamustine followed by Obinutuzumab (GA101), Zanubrutinib (BGB-3111) and Venetoclax (ABT-199) in patients with relapsed/refractory CLL - (CLL2-BZAG) - CLL2-BZAG

niversity Of Cologne0 sites42 target enrollmentMay 2, 2024

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: niversity Of Cologne
Enrollment: 42
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

May 2, 2024

End Date

TBD

Last Updated

last year

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

niversity Of Cologne

Eligibility Criteria

Inclusion Criteria

•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

Exclusion Criteria

•(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).