A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CELESTIAL-RRCLL)

Browse trials for

• Leukemia, Lymphocytic, Chronic, B-Cell 1,603

Keywords

• B-cell lymphoma 2 inhibitor (BCL-2i)
• CLL-RR1
• German CLL Study Group

Study arms

• Experimental
  Arm A: Sonrotoclax plus Obinutuzumab

  Sonrotoclax and obinutuzumab will be administered in combination.

  Drug: Sonrotoclax · Drug: Obinutuzumab

• Experimental
  Arm B: Sonrotoclax plus Rituximab

  Sonrotoclax and rituximab will be administered in combination.

  Drug: Sonrotoclax · Drug: Rituximab

• Experimental
  Arm C: Sonrotoclax plus Obinutuzumab (MRD)

  Sonrotoclax and obinutuzumab will be administered in combination with treatment guided by evaluation of minimal residual disease (MRD).

  Drug: Sonrotoclax · Drug: Obinutuzumab

• Active comparator
  Arm D: Venetoclax plus Rituximab

  Venetoclax and rituximab will be administered in combination.

  Drug: Rituximab · Drug: Venetoclax

Interventions

• DrugSonrotoclax

  Administered orally

  Also known as: BGB-11417

• DrugObinutuzumab

  Administered intravenously

  Also known as: Gazyva

• DrugRituximab

  Administered intravenously

  Also known as: Rituxan

• DrugVenetoclax

  Administered Orally

  Also known as: Venclexta

Primary outcomes

1. Progression-Free Survival (PFS) as assessed by Blinded Independent Review Committee (BIRC) for Arm A versus Arm D

   PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

   Time frame: Up to approximately 51 months

Secondary outcomes

1. Progression-Free Survival (PFS) as assessed by BIRC for Arm B versus Arm D

   PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

   Time frame: Up to approximately 69 months

2. Rate of uMRD4 for Arm A versus Arm D

   The rate of undetectable minimal residual disease (uMRD4) in peripheral blood based on next-generation sequencing (NGS)

   Time frame: Up to approximately 12 months

3. Complete Response Rate as assessed by BIRC for Arm A versus Arm D

   Complete Response Rate (CRR) is defined as the percentage of participants that achieve a best response of complete response (CR) or complete response with incomplete hematopoietic recovery (CRi)

   Time frame: Up to approximately 25 months

4. Overall Survival for Arm A versus Arm D

   Overall survival (OS) is defined as the time from the date of randomization to the date of death

   Time frame: Up to approximately 84 months

5. PFS per Investigator Assessment (INV) for Arm B versus Arm D

   PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

   Time frame: Up to approximately 69 months

6. CRR per BIRC and by INV for Arm B versus Arm D

   CRR is defined as the percentage of participants that achieve a best response of CR or CRi

   Time frame: Up to approximately 25 months

7. OS for Arm B versus Arm D

   OS is defined as the time from the date of randomization to the date of death

   Time frame: Up to approximately 84 months

8. Rate of uMRD4 for Arm B versus Arm D

   The rate of uMRD4 in peripheral blood based on NGS

   Time frame: Up to approximately 25 months

9. PFS per BIRC and by INV for Arm A versus Arm B

   PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

   Time frame: Up to approximately 69 months

10. CRR per BIRC and by INV for Arm A versus Arm B

    CRR is defined as the percentage of participants that achieve a best response of CR or CRi

    Time frame: Up to approximately 25 months

11. OS for Arm A versus Arm B

    OS is defined as the time from the date of randomization to the date of death

    Time frame: Up to approximately 84 months

12. Rate of uMRD4 for Arm A versus Arm B

    The rate of uMRD4 in peripheral blood based on NGS

    Time frame: Up to approximately 25 months

13. Rate of uMRD4 for Arm A versus Arm D

    The rate of uMRD4 in peripheral blood based on NGS

    Time frame: Up to approximately 25 months

14. CRR per INV for Arm A versus Arm D

    CRR is defined as the percentage of participants that achieve a best response of CR or CRi

    Time frame: Up to approximately 25 months

15. PFS per INV for Arm A versus Arm D

    PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

    Time frame: Up to approximately 51 months

16. PFS per INV for Arm C versus Arm D

    PFS is defined as the time from randomization to the date of progression or death, whichever occurs first.

    Time frame: Up to approximately 69 months

17. CRR per INV for Arm C versus Arm D

    CRR is defined as the percentage of participants that achieve a best response of CR or CRi

    Time frame: Up to approximately 25 months

18. OS for Arm C versus Arm D

    OS is defined as the time from the date of randomization to the date of death

    Time frame: Up to approximately 84 months

19. Rate of uMRD4 for Arm C versus Arm D

    The rate of uMRD4 in peripheral blood based on NGS

    Time frame: Up to approximately 25 months

20. Overall Response Rate (ORR) per BIRC and by INV

    ORR is defined as the percentage of participants that achieve a best response of partial response (PR) or better

    Time frame: Up to approximately 25 months

21. Duration of Response (DOR) per BIRC and by INV

    DOR is defined as the time from the date that response criteria were first met to the date of first documentation of disease progression or death, whichever occurs first

    Time frame: Up to approximately 69 months

22. Time to Response (TTR) per BIRC and by INV

    TTR is defined as the time from the date of randomization to the date response criteria were first met

    Time frame: Up to approximately 25 months

23. Time to Next Anti-CLL/SLL Treatment (TTNT)

    TTNT is defined as the time from the date of randomization to the date of next anti-CLL/SLL treatment

    Time frame: Up to approximately 84 months

24. Rate of uMRD4

    The rate of uMRD4 in peripheral blood based on NGS

    Time frame: Up to approximately 25 months

25. Change from Baseline in the European Organisation of Research and Treatment of Cancer-Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Global Health Status/Quality of Life and Physical Functioning Scales

    The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best). Higher scores in global health status (GHS) and functional scales indicate better health-related quality of life (HRQoL).

    Time frame: Baseline and up to approximately 69 months

26. Change from Baseline in EORTC QLQ for Chronic Lymphocytic Leukemia (EORTC QLQ-CLL17) Symptom Burden and Fatigue Scales

    The EORTC QLQ-CLL17 is the CLL module of QLQ-C30 consisting of 17 items and comprising 3 scales: symptom burden due to disease and/or treatment (6 items), physical condition/fatigue (4 items), and worries/fears about health and functioning (7 items) Items are rated using a 4-point response scale ("not at all," "a little," "quite a bit," and "very much") and the recall period for all items is the past 7 days. Lower scores indicate better HRQoL.

    Time frame: Baseline and up to approximately 69 months

27. Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Number of participants with TEAEs, including laboratory values, vital signs, and physical examination findings, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

    Time frame: From the first dose of study drug(s) to 30 days after the last dose of sonrotoclax or venetoclax, or 90 days after the last dose of obinutuzumab or rituximab; up to approximately 26 months

Individual participant data

Plan to share: Yes — BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

Supporting information: Study protocol, Sap, Csr