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CLL (Chronic Lymphocytic Leukemia)Phase 2NCT07899398

A Trial to Evaluate the Efficacy and Safety of a Fitness-adapted Thera-py Approach With Either Continuous Zanubrutinib Monotherapy or Time-limited Zanubrutinib + Sonrotoclax in Older and/or Frail Patients With Treatment-naïve CLL

A Phase 2 study testing Zanubrutinib and Sonrotoclax in people with CLL (Chronic Lymphocytic Leukemia), run by German CLL Study Group.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

The CLL-Frail2 trial will be a prospective, open-label, multicentre phase-II-trial to evaluate the efficacy and safety of a fitness-adapted therapy approach with either con-tinuous zanubrutinib (BGB-3111) monotherapy or time-limited zanubrutinib + sonrotoclax (BGB-11417) in older (aged ≥80 years) and/or frail patients… Read more about this study

Who is it for?
Any age
Conditions the study is for
CLL (Chronic Lymphocytic Leukemia)
What is being tested?
Zanubrutinib and Sonrotoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
No sites listed yet
Study dates
1 Dec 2026to 1 Jan 2031
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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥80 years OR considered frail defined by a frailty score of >2 on the FRAIL s-Scale via the patient´s assessment
  • Hasve documented treatment-naïve CLL or small lymphocytic lymphoma (SLL) according to iwCLL 2018 criteria4
  • CLL/SLL requiring treatment according to the iwCLL 2018 criteria4
  • Adequate marrow function independent of growth factor or transfusion support within 2 weeks of screening as follows, unless cytopenia is due to marrow involvement of CLL:
  • Absolute neutrophil count ≥ 1.0 × 10^9/L
  • Platelet counts ≥ 30 × 10^9/L; in cases of thrombocytopenia clearly due to marrow in-volvement of CLL (per the discretion of the investigator); platelet count should be ≥ 10 × 10^9/L if there is bone marrow involvement
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  • Total haemoglobin ≥ 9 g/dL (without transfusion support, unless anaemia is due to mar-row involvement of CLL)
  • Adequate liver function as indicated by a total bilirubin, AST, and ALT ≤2 times the institutional upper limit of normal (ULN) value unless directly attributable to the patient's CLL or Gilbert's syndrome
  • 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 repeatedly until 6 months after last month of treatment), negative testing for hepa-titis C RNA within 6 weeks prior to registration.
  • Life expectancy ≥ 3 months
  • In case of a recent previous (i.e. debulking) treatment, patients must have recovered from acute toxicities and treatment regimen must be stopped within the following time periods be-fore start of the study treatment in the CLL-Frail2 trial • chemotherapy ≥ 28 days
  • antibody treatment ≥ 14 days
  • corticosteroids may be applied until the start of the study therapy, these have to be re-duced to an equivalent of ≤ 20mg prednisolone per day during treatment
  • Signed informed consent and, in the investigator's judgment, able to comply with the study protocol
  • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements

Who cannot join

  • 1. Pprevious CLL-directed therapies. 2. Transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leu-kaemia).
  • 3. Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML).
  • 4. Uncontrolled autoimmune condition. 5. Malignancies other than CLL currently requiring systemic therapies (unless the malignant dis-ease is in a stable remission at the discretion of the treating physician).
  • 6. Uncontrolled infection currently requiring systemic treatment. 7. Any serious medical condition or abnormality in clinical laboratory tests that, in the investiga-tor's judgment, precludes the patient's safe participation in and completion of the study.
  • 8. Requirement of therapy with strong CYP3A4 inhibitors/ inducers. 9. Requirement of therapy with phenprocoumon or other vitamin K antagonists. 10. 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 antibody (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 for HBV reactivation.
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  • Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.
  • 11. Major surgery within 4 weeks of the first dose of study drug. 12. Any uncontrolled or clinically significant cardiovascular disease including the following:
  • New York Heart Association class III or IV congestive heart failure
  • History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricu-lar fibrillation, torsades de pointes) 13. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand dis-ease, or history of spontaneous bleeding requiring blood transfusion or other medical inter-vention.
  • 14. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
  • 15. Severe or debilitating pulmonary disease. 16. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery proce-dures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • 17. 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.
  • 18. Known hypersensitivity to zZanubrutinib or sonrotoclax or any of the excipients.
  • 19. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment).
  • 20. 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 contra-ceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 90 days after sonrotoclax and 30 days after zanubrutinib respec-tively. Vaccination with a live vaccine <28 days prior to randomizationregistration.
  • 21. Vaccination with a live vaccine <28 days prior to randomizationregistration.
  • 22. Legal incapacity. 23. Prisoners or subjects who are institutionalized by regulatory or court order.
  • 24. Persons who are in dependence to the sponsor or an investigator.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Florian Simon, DR. MED. contact

+49 221 478 88220

florian.simon@uk-koeln.de

About this study

Official title: A Prospective, Open-label, Multicentre Phase-II-trial to Evaluate the Efficacy and Safety of a Fitness-adapted Therapy Approach With Either Continuous Zanubrutinib (BGB-3111) Monotherapy or Time-limited Zanubrutinib + Sonrotoclax (BGB-11417) in Older (Aged ≥80 Years) and/or Frail Patients With Treatment-naïve Chronic Lymphocytic Leukemia (CLL)

The CLL-Frail2 trial will be a prospective, open-label, multicentre phase-II-trial to evaluate the efficacy and safety of a fitness-adapted therapy approach with either con-tinuous zanubrutinib (BGB-3111) monotherapy or time-limited zanubrutinib + sonrotoclax (BGB-11417) in older (aged ≥80 years) and/or frail patients with treatment-naïve CLL. The primary objective of the study is to evaluate the efficacy and safety of fitness-adapted therapy in older (aged ≥80 years) and/or frail patients with treatment-naïve CLL.

Being tested
Zanubrutinib, Sonrotoclax
Medical subject headings
Leukemia, B-Cell

What participants receive

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

  • ZanubrutinibBiological

    Zanubrutinib maintainance + run-in

  • SonrotoclaxDrug

    12 cycles sonrotoclax infusion

Study groups in NCT07899398
Study groupRoleWhat they receive
Arm A - ZanubrutinibExperimentalZanubrutinib daily dosage p.o. of 320 mg (max. 12 cycles)
Receives: Biological: Zanubrutinib
Arm B - Zanubrutinib/SonrotoclaxExperimentalZanubrutinib daily dosage of 320 mg p.o. + 5 week ramp-up of Sonrotoclax to a max. dose of 320 mg daily p.o. (max. 12 cycles)
Receives: Biological: Zanubrutinib; Drug: Sonrotoclax

What is being measured

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

  1. Progression-free survival (PFS)

    Measured: up to 24 months after the last patient was entrolled

Secondary outcomes (7)

  1. Overall response rate (ORR) and complete response (CR) rate (CRR) at the final restaging

    Measured: at final restaging and further timepoints up to 24 months after end of treatment

  2. Best response assessed until 1 year after end of treatment

    Measured: up to 24 months after end of treatment

  3. Duration of response (DOR)

    Measured: up to 24 months after end of treatment

  4. Time to next treatment (TTNT)

    Measured: up to 24 months after end of treatment

  5. Safety parameters: type, frequency and severity of - adverse events (AEs) - adverse events of special interest (AESI) - adverse events of particular interest (AEPI)

    Measured: up to 24 months after end of treatment

  6. Overall survival (OS)

    Measured: up to 24 months after end of treatment

  7. Undetectable Mmeasurable residual disease (uMRD) levelrates by the following different types of measurement from the following materials: flow cytometry from peripheral blood (PB) at the final restaging in all patients receiving fixed-duration therap

    Measured: up to 24 months after end of treatment

Timeline

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

  1. First posted27 Oct 2026
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion1 Jan 2029 (estimated)
  4. Study completion1 Jan 2031 (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
Parallel groups
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07899398
Sponsor's protocol ID
CLL-FRAIL2
Status last verified
Oct 2026
First submitted
3 Dec 2025
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib and Sonrotoclax in people with CLL (Chronic Lymphocytic Leukemia), run by German CLL Study Group.

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 15 inclusion and 21 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: opening soon, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

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 Florian Simon, DR. MED. (+49 221 478 88220, florian.simon@uk-koeln.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: up to 24 months after the last patient was entrolled). 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 NCT07899398.

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 27 Oct 2026.

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