Evaluation of a treatment with bendamustine, followed by obinutuzumab,zanubrutinib and venetoclax in patients with relapsed chronic lymphocyticleukemia
- Conditions
- Patients with relapsed/refractory CLL requiring treatmentMedDRA version: 21.1Level: PTClassification code 10008958Term: Chronic lymphocytic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003270-27-DE
- Lead Sponsor
- niversität zu Köln B.1.2
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1.Relapsed/refractory CLL in need of treatment according to iwCLL criteria3
In case of a recent previous treatment, patients must have recovered from acute toxicities and treatment regi-men 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 inhibi-tor, 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 in-tolerance to ibrutinib are eligible for participation.
2.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
3.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 attributa-ble to the patient´s CLL (e.g. bone marrow infiltration), in this case, platelet count should be = 10 × 109/L.
4.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
5.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), nega-tive testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
6.Age = 18 years
7.ECOG 0 to 2, ECOG 3 is only permitted if related to CLL (e.g. due to anemia or severe constitutional symptoms)
8.Life expectancy = 6 months
9.Ability and willingness to provide written informed con-sent and to adhere to the study visit schedule and other protocol requirements
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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
1.(Suspicion of) transformation of CLL (i.e. Richter’s trans-formation, pro-lymphocytic leukemia) or central nervous system (CNS) involvement
2.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)
3.Confirmed progressive multifocal leukoencephalopathy (PML)
4.Malignancies other than CLL currently requiring systemic therapies
5.Uncontrolled infection requiring systemic treatment
6.Any comorbidity or organ system impairment rated with a CIRS (cumulative illness rating scale) score of 4, exclud-ing 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, inabil-ity to swallow tablets or impaired resorption in the gastro-intestinal tract)
7.Significantly increased risk of bleeding according to the investigator´s evaluation, e.g. due known bleeding diath-esis (e.g. von-Willebrandt´s disease or hemophilia), major surgical procedure = 4 weeks or stroke/intracranial hemor-rhage = 6 months.
8.Requirement of therapy with strong CYP3A4 inhibi-tors/inducers or anticoagulant with phenprocoumon (mar-cumar) or other vitamin K-antagonists
9.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).
10.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 re-ceive a debulking with bendamustine
11.Pregnant women and nursing mothers (a negative preg-nancy test is required for all women of childbearing po-tential within 7 days before start of treatment)
12.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 contracep-tion 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.
13.Vaccination with a live vaccine = 28 days prior to registra-tion
14.Legal incapacity
15.Prisoners or subjects who are institutionalized by regula-tory or court order
16.Persons who are in dependence to the sponsor or an in-vestigator
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