Efficacy and Safety of Zanubrutinib Plus Tislelizumab for Treatment of Patients With Richter Transformation

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the CLL-RT1 trial is to evaluate the efficacy and safety of zanubrutinib (BGB-3111), a BTK inhibitor plus tislelizumab (BGB-A317), a PD1 inhibitor for treatment of patients with Richter Transformation

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: German CLL Study Group
• Treatments: Zanubrutinib

Criteria

Inclusion Criteria:

1. Confirmed diagnosis of CLL according to iwCLL criteria (Hallek et al, 2018)

2. Confirmed histopathological diagnosis of RT

3. Creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection

4. Adequate liver function as indicated by a total bilirubin ≤ 2x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly 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

5. Negative serological testing for hepatitis B (HBsAg negative 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

6. Age at least 18 years

7. 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)

8. Life expectancy ≥ 6 months

9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

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 graft-versus-host disease (GVHD) after prior allogeneic stem cell transplantation within any time

4. Patients with confirmed progressive multifocal leukoencephalopathy (PML)

5. Uncontrolled autoimmune condition

6. Malignancies other than CLL currently requiring systemic therapies

7. Active infection currently requiring systemic treatment

8. Any comorbidity or organ system impairment rated with a Cumulative Illness Rating Scale (CIRS) 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