Patients with previously untreated Richter Transformation or patients who responded to up to one prior line of RT therapy MedDRA version: 21.0 Level: LLT Classification code 10008975 Term: Chronic lymphocytic leukaemia variants System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tislelizumab
Product Name: Tislelizumab
Product Code: BGB-A317
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
Trade Name: Zanubrutinib
Product Name
Sponsors
Universität zu Köln
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Confirmed diagnosis of CLL according to iwCLL criteria (Hallek et al, 2018) [13] 2. Confirmed histopathological diagnosis of RT (diffuse large B-cell lymphoma or Hodgkin’s lymphoma [Hodgkin’s lym-phoma only when not eligible for more intensive treatment]) 3. Previously untreated RT or patients with objective response or non-tolerance to first-line RT treatment 4. Creatinine clearance =30ml/min calculated according to the modified formula of Cockcroft and Gault or directly meas-ured with 24hr urine collection or an eqivalent method 5. Adequate liver function as indicated by a total bilirubin= 2 x, AST/ALT = 2.5 x the institutional ULN value, unless di-rectly attributable to the patient’s CLL/RT or to Gilbert’s Syndrome, in which case a max. total bilirubin = 4 x and AST/ALT = 5 x the institutional ULN value are required. 6. 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 two months until 2 months after last dose of zanubrutinib), negative testing for hepati-tis-C RNA and negative HIV test within 6 weeks prior to reg-istration 7. Age at least 18 years 8. ECOG performance status 0-2, ECOG 3 is only permitted if related to CLL or RT (e.g. due to anaemia or severe consti-tutional symptoms) 9. Life expectancy = 3 months 10. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other proto-col requirements Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: Exclusion criteria 1. Patients who did not respond to previous line of RT therapy (i.e. primary progressive patients) 2. Patients with more than one prior line of RT therapy 3. Allogenic stem cell transplantation within the last 100 days or signs of active GVHD after prior allogeneic stem cell transplantation within any time 4. Patients with confirmed PML 5. Uncontrolled autoimmune condition 6. Malignancies other than CLL currently requiring systemic therapies (unless the malignant disease is in a stable remission at the discretion of the treating physician) 7. Active infection currently requiring systemic treatment 8. 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 comprise the patients safety or interfere with the absorption or metabolism of the study drugs 9. Requirement of therapy with strong CYP3A4 inhibitors/ inducers 10. Requirement of therapy with phenprocoumon or other vitamin K antagonists. 11. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life [t1/2] of the compound, whichever is longer) prior to registration 12. Known hypersensitivity to tislelizumab, zanubrutinib or any of the excipients 13. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment) 14. 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 contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 12 months after the end of study treatment. 15. Vaccination with a live vaccine <28 days prior to randomization 16. Legal incapacity 17. Prisoners or subjects who are institutionalized by regulatory or court order 18. Persons who are in dependence to the sponsor or an investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of a combinational therapy with tislelizumab and zanubrutinib in CLL pa-tients with Richter transformation to DLBCL.;Secondary Objective: The secondary objective is to evaluate the safety of combinational therapy with tislelizumab and zanubrutinib in CLL patients with Richter transformation to DLBCL.;Primary end point(s): Overall response rate (ORR) after induction therapy (i.e. 6 cycles) according to the refined Lugano Classification (Cheson et al, 2016). -Complete response (CR) -Partial response (PR) | — |
Countries
Austria, Denmark, Germany
Contacts
Public ContactInformation Desk
German CLL Study Group
Outcome results
None listed