AzTrials
AzTrials

Richter TransformationPhase 2CLL-RT1NCT04271956

Efficacy and Safety of Zanubrutinib Plus Tislelizumab Treatment With or Without Sonrotoclax for Patients With Richter Transformation

A Phase 2 study testing Tislelizumab, Zanubrutinib and Sonrotoclax in people with Richter Transformation, run by German CLL Study Group at 11 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Richter Transformation
What is being tested?
Tislelizumab, Zanubrutinib and Sonrotoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
11 sitesin 3 countries
Study dates
19 Feb 2020to Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of CLL according to iwCLL criteria (Hallek et al, 2018)
  • Confirmed histopathological diagnosis of RT (diffuse large B-cell lymphoma or Hodgkin's lymphoma [Hodgkin's lymphoma only when not eligible for more in-tensive treatment])
  • Previously untreated RT or patients with objective response or non-tolerance to first-line RT treatment
  • Adequate bone marrow function as defined by:
  • Absolute neutrophil count (ANC) ≥ 1000/mm3, except for patients with bone marrow involvement in which ANC must be ≥ 500/mm3
  • Platelet ≥ 75,000/mm3, except for patients with bone marrow involvement in which the platelet count must be ≥ 30,000/mm3
Show all 13Show fewer
  • Creatinine clearance ≥30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection or an equivalent method.
  • Adequate liver function as indicated by a total bilirubin≤ 2 x, 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 ≤ 3 x and AST/ALT ≤ 5 x the institutional ULN value are required.
  • Negative serological testing for hepatitis B (HBsAg negative and anti-HBc nega-tive; 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 af-ter last dose of zanubrutinib), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration
  • Age at least 18 years
  • 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)
  • Life expectancy ≥ 3 months
  • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Who cannot join

  • Patients who did not respond to previous line of RT therapy (i.e. primary progressive patients)
  • Patients with more than one prior line of RT therapy
  • Allogenic stem cell transplantation within the last 100 days or signs of active GVHD after prior allogeneic stem cell transplantation within any time
  • Patients with confirmed PML
  • Uncontrolled autoimmune condition
  • Malignancies other than CLL currently requiring systemic therapies (unless the malignant disease is in a stable remission at the discretion of the treating phy-sician)
Show all 33Show fewer
  • Uncontrolled infection currently requiring systemic treatment
  • Any comorbidity or organ system impairment rated with a CIRS (cumulative ill-ness 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
  • Requirement of therapy with strong CYP3A4 inhibitors/ inducers
  • Requirement of therapy with phenprocoumon or other vitamin K antagonists.
  • Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
  • Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core anti-body (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (< 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation.
  • Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
  • Major surgery within 4 weeks of the first dose of study drug.
  • Any uncontrolled or clinically significant cardiovascular disease including the following:
  • Myocardial infarction within 6 months before screening
  • Unstable angina within 3 months before screening
  • New York Heart Association class III or IV congestive heart failure
  • History of clinically significant arrhythmias (eg, sustained ventricular tachy-cardia, ventricular fibrillation, torsades de pointes)
  • History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood trans-fusion or other medical intervention
  • History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
  • Severe or debilitating pulmonary disease
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • 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
  • Known hypersensitivity to tislelizumab, zanubrutinib, sonrotoclax or any of the excipients
  • 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 ef-fective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 6 months after the end of study treatment.
  • Vaccination with a live vaccine <28 days prior to randomization
  • Legal incapacity
  • Prisoners or subjects who are institutionalized by regulatory or court order
  • Persons who are in dependence to the sponsor or an investigator

Trial locations and contacts

11 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Barbara Eichhorst, Prof. contact

+4922147888220

barbara.eichhorst@uk-koeln.de

Othman Al-Sawaf, MD contact

+4922147888220

othman.al-sawaf@uk-koeln.de

11 sites in 3 countries

Germany9 sites, 9 recruiting

  • Charité Berlin

    Berlin, State of Berlin, 12203

    Not yet recruiting

  • Uniklinik Köln

    Cologne, 50937

    Recruiting

  • Universitätsklinikum Carl Gustav Carus

    Dresden, 01307

    Recruiting

  • Universitätsklinikum Essen

    Essen, 45147

    Recruiting

  • Universitätsklinikum Schleswig-Holstein Campus Kiel

    Kiel, 24105

    Recruiting

  • H.O.T Praxis Landshut

    Landshut, 84036

    Recruiting

  • Brüderkrankenhaus St. Josef Paderborn

    Paderborn, 33098

    Recruiting

  • Universitätsmedizin Rostock

    Rostock, 18057

    Recruiting

  • Universitätsklinik Ulm

    Ulm, 89081

    Recruiting

Other trials in Germany

Austria1 site, 1 recruiting

  • Allgemeines Krankenhaus der Stadt Wien

    Vienna, 1090

    Recruiting

Other trials in Austria

Denmark1 site, 1 recruiting

  • Rigshospitalet

    Copenhagen, 2100

    Recruiting

Other trials in Denmark

About this study

Official title: A Prospective, Open-label, Multicenter Phase-II Trial 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 With or Without Sonrotoclax（BGB-11417), a Bcl-2 Inhibitor (CLL-RT1-trial of the GCLLSG).

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

Read the detailed description

Richter Transformation (RT) remains one of the biggest challenges in the treatment and management of CLL. While considerable progress has been made in the treatment of CLL, the prognosis of CLL patients with malignant disease transformation still is very poor and reported median OS is between 6 to 8 months. Conventional approaches with chemo- and chemoimmunotherapy have largely failed to improve response rates in RT patients. However, as the established treatment approach for de-novo Diffuse Large B Cell Lymphoma (DLBCL) is chemoimmunotherapy with a combination of Rituximab, Cyclophosphamid, Hydroxydaunorubicin, Vincristin and Prednisolon (R-CHOP), this has become the most commonly used regimen for lack of alternative strategies, despite poor efficacy. Patients being fit enough for allogeneic transplantation are undergoing this procedure after induction with R-CHOP. However, the majority of patients are not suitable for transplantation and relapse quickly. Hence, there is urgent need to improve therapy of RT by testing new compounds and combinations for treatment of this disease. Based on the available preclinical and preliminary clinical data on checkpoint inhibition plus Bruton's tyrosine (BTK) inhibition, the current trial will systematically assess the safety and toxicity of tislelizumab, a programmed cell death protein 1 (PD-1) inhibitor, plus zanubrutinib, a BTK inhibitor in patients with RT.

Being tested
Tislelizumab, Zanubrutinib, Sonrotoclax

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TislelizumabBiological

    Also called BGB-A317

    Cycle (q21d): Day 1: Tislelizumab i.v. 200 mg

  • ZanubrutinibDrug

    Also called BGB-3111

    Cycle (q21d): Zanubrutinib p.o. 160 mg twice a day

  • SonrotoclaxDrug

    Also called BGB-11417

    Cycle 1: Sonrotoclax Start Ramp-up to 320 mg QD po Days 1-2 Sonrotoclax 2 mg (2 tabl. at 1mg) Days 3-4 Sonrotoclax 5 mg (1 tabl. at 5mg) Days 5-6 Sonrotoclax 10 mg (2 tabl. at 5mg) Days 7-8 Sonrotoclax 20 mg (1 tabl. at 20mg) Days 9-10 Sonrotoclax 40 mg (2 tabl. at 20mg) Days 11-12 Sonrotoclax 80 mg (1 tabl. at 80mg) Days 13-14 Sonrotoclax 160 mg (2 tabl. at 80mg) Days 15-16 Sonrotoclax 320 mg (4 tabl. at 80mg)

    Cycle 2-6: Day 1-21 Sonrotoclax 320 mg QD po

Study groups in NCT04271956
Study groupRoleWhat they receive
Tislelizumab + ZanubrutinibExperimentalInduction: 6 cycles (q21d) of Tislelizumab + Zanubrutinib Consolidation: 6 cycles (q21d) of Tislelizumab + Zanubrutinib Maintenance: Patients with response to therapy continue to take Tislelizumab + Zanubrutinib (Q3W) until disease progression, non-tolerance or when receiving allogeneic stem cell transplantation (SCT) for consolidation
Receives: Biological: Tislelizumab; Drug: Zanubrutinib
Tislelizumab + Zanubrutinib + SonrotoclaxExperimentalInduction: 6 cycles (q21d) of Tislelizumab + Zanubrutinib + Sonrotoclax Consolidation: 6 cycles (q21d) of Tislelizumab + Zanubrutinib + Sonrotoclax Maintenance: Patients with response to therapy continue to take Tislelizumab + Zanubrutinib (Q3W) + Sonrotoclax until disease progression, non-tolerance or when receiving allogeneic stem cell transplantation (SCT) for consolidation
Receives: Biological: Tislelizumab; Drug: Zanubrutinib; Drug: Sonrotoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR) after induction therapy according to the refined Lugano Classification (Cheson et al, 2016)

    Proportion of patients having achieved complete response (CR) or partial response (PR)

    Measured: 18 weeks

Secondary outcomes (7)

  1. ORR after induction therapy according to the IWCLL criteria (Hallek et al, 2018)

    Proportion of patients having achieved complete response (CR) or partial response (PR)

    Measured: 18 weeks

  2. ORR after consolidation therapy

    Proportion of patients having achieved complete response (CR) or partial response (PR)

    Measured: 36 weeks

  3. Progression-free Survival (PFS)

    Time from the date of registration to the date of first occurrence of disease progression or relapse (determined according to the IWCLL guidelines and Lugano classification) or death from any cause, whichever occurs first

    Measured: Up to 15 months

  4. Overall Survival (OS)

    Time from the date of registration to the date of death due to any cause

    Measured: Up to 15 months

  5. Time to Next Treatment (TTNT)

    Time from date of registration to the date of first subsequent CLL/RT treatment

    Measured: Up to 15 months

  6. Duration of response

    Time from the date of first documented response to the first occurrence of progression, relapse or death by any cause, whichever occurs first.

    Duration of response will be evaluated both according to the refined Lugano Classification as well as according to the IWCLL criteria. In the first case it will be calculated for patients with CR or PR, in the second case for patients with (clin.) CR, (clin.) CRi, PR, or PR-L.

    Measured: Up to 15 months

  7. Type, frequency, severity of adverse events (AEs)

    Measured: Up to 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2020
  2. Study start19 Feb 2020
  3. Primary completionAug 2027 (estimated)
  4. Study completionAug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Recruitment in cohort 1 (double combination therapy) has already been completed. Recruitment in new cohort 2 (triple combination therapy) will start in Q3 2024.
Masking
None (open label)
Enrolment
83 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04271956
Sponsor's protocol ID
CLL-RT1
Other IDs
2023-504653-12-00, 2023
Acronym
CLL-RT1
Status last verified
Aug 2026
First submitted
14 Feb 2020
Last updated
20 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Al-Sawaf O, Ligtvoet R, Robrecht S, Stumpf J, Fink AM, Tausch E, Schneider C, Boettcher S, Mikusko M, Ritgen M, Schetelig J, von Tresckow J, Vehling-Kaiser U, Gaska T, Wendtner CM, Chapuy B, Fischer K, Kreuzer KA, Stilgenbauer S, Staber P, Niemann C, Hallek M, Eichhorst B. Tislelizumab plus zanubrutinib for Richter transformation: the phase 2 RT1 trial. Nat Med. 2024 Jan;30(1):240-248. doi: 10.1038/s41591-023-02722-9. Epub 2023 Dec 9.

    PubMed 38071379

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tislelizumab, Zanubrutinib and Sonrotoclax in people with Richter Transformation, run by German CLL Study Group at 11 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Germany, Austria, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Barbara Eichhorst, Prof. (+4922147888220, barbara.eichhorst@uk-koeln.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) after induction therapy according to the refined Lugano Classification (Cheson et al, 2016) (time frame: 18 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04271956, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in