Evaluation of a Treatment with tislelizumab and zanubrutinib in patients with a Richter Transformation.
- Conditions
- Patients excluded are:-Primary progressive patients, i.e. patients who did not respond to their first-line treatment (=> Exclusion criteria 1)-Patients with 2 or more prior lines of therapy (=> Exclusion criteria 2) Two groups of patients with RT are eligible (=> Inclusion criteria 3):- Patients without previous treatment- Patients with 1 prior line of therapy only if they responded to therapyMedDRA version: 21.0Level: LLTClassification code 10008975Term: Chronic lymphocytic leukaemia variantsSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002492-17-DK
- Lead Sponsor
- niversität zu Köln
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 48
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 lymphoma 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 measured 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 hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
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 constitutional 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 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 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24
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, 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 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 vit-amin 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 preg-nancy 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 meno-pause, 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 af-ter the end of study treatment.
15.Vaccination with a live vaccine <28 days prior to randomi-zation
16.Legal incapacity
17.Prisoners or subjects who are institutionalized by regula-tory or court order
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: After induction therapy (i.e. 6 cycles);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).<br>-Complete response (CR) <br>-Partial response (PR) <br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •ORR after induction therapy (i.e. 6 cycles) according to IWCLL criteria (Hallek et al, 2018)<br>•ORR after consolidation therapy (i.e. 12 cycles)<br>•Duration of response<br>•Progression-free survival (PFS)<br>•Overall survival (OS)<br>•Time to next treatment (TTNT)<br>•Proportion of patients receiving SCT for consolidation<br>•Exploratory endpoints: Evaluation of relationship between various baseline markers, including PD-1/PD-L1 expression and mutational load, and clinical outcome parameters<br>•Safety parameters: type, frequency, severity of adverse events (AEs), and their relationship to study treatment<br>;Timepoint(s) of evaluation of this end point: ORR after induction therapie (i.e. 6 cycles)<br>ORR after consolidation therapy (i.e. 12 cycles)