Waldenstrom Macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent, Waldenstrom's Macroglobulinemia Refractory
Conditions
Keywords
Waldenström's macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent, Waldenstrom's Macroglobulinemia Refractory, Lymphoma, BGB-11417, BCL-2i
Brief summary
This study will evaluate the safety and efficacy of the BCL2 inhibitor sonrotoclax (BGB-11417) in participants with relapsed/refractory Waldenström's Macroglobulinemia (R/R WM) and in combination with zanubrutinib in adult participants with previously untreated WM.
Detailed description
This study will test whether sonrotoclax (BGB-11417) can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) both when used alone in those who have not responded well to conventional treatments and when used in combination with zanubrutinib in those who have not yet received treatment. The main goals of the study are to determine how many participants no longer have evidence of cancer or have some improvement in the signs and symptoms of cancer after treatment, and to determine what adverse events, or side effects, participants might experience. BCL2 is a key protein involved in cell death, and abnormal levels of BCL2 are associated with many cancers. Blocking the action of BCL2 proteins is a promising approach with potential therapeutic benefits in participants with different types of cancers, including WM. This study will enroll approximately 105 participants. All participants will receive sonrotoclax orally as a tablet. The study will take place at multiple centers worldwide. The overall time to participate in this study is approximately 5 years. Note: Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGSonrotoclax
Administered orally as a tablet.
DRUGZanubrutinib
Administered orally as a capsule.
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical and definitive histologic diagnosis of WM. * Meeting ≥ 1 criterion for treatment according to consensus panel criteria from the 2nd International Workshop on Waldenström's Macroglobulinemia (IWWM). * For Cohorts 1-3, refractory or relapsed disease at study entry unless participants had intolerance to the most recent therapy. Refractory disease is defined as not attaining at least a major response, or progressing while on or within 6 months of completing therapy. Relapsed disease is defined as attaining at least a major response to therapy and meeting the criteria for disease progression beyond 6 months after completing therapy. * For Cohort 4, patients must not have received prior therapy for WM (except for plasmapheresis). * Adequate organ function.
Exclusion criteria
* Central nervous system (CNS) involvement by WM. * Transformation to aggressive lymphoma, such as diffuse large B-cell lymphoma. * History of other malignancies ≤ 2 years before study entry. * Uncontrolled active systemic infection or recent infection requiring parenteral antimicrobial therapy that was completed ≤ 14 days before the first dose of the study drug. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Major Response Rate (MRR) | Up to approximately 4 years | MRR is defined as the percentage of participants achieving partial response (PR) or better, as assessed by the Independent Review Committee (IRC) per the 11th International Workshop on Waldenström Macroglobulinemia (IWWM-11) WM response criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cohorts: MRR as assessed by the Investigator | Up to approximately 5 years | MRR is defined as the percentage of participants achieving PR or better. |
| Cohorts 1, 2, and 3: Duration of Major Response (DoMR) as assessed by the IRC | Up to approximately 5 years | DoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first. |
| All Cohorts: DoMR as assessed by the Investigator | Up to approximately 5 years | DoMR is defined as the time from first determination of major response until first documentation of progression or death, whichever occurs first. |
| Cohorts 1, 2, and 3: Complete Response (CR) + Very Good Partial Response (VGPR) as assessed by the IRC | Up to approximately 5 years | CR + VGPR is defined as the percentage of participants who achieve CR or VGPR. |
| All Cohorts: CR + VGPR as assessed by the Investigator | Up to approximately 5 years | CR + VGPR is defined as the percentage of participants who achieve CR or VGPR. |
| Cohorts 1, 2, and 3: Overall Response Rate (ORR) as assessed by the IRC | Up to approximately 5 years | ORR is defined as the percentage of participants with minor response (MR) or better. |
| All cohorts: ORR as assessed by the investigator | Up to approximately 5 years | ORR is defined as the percentage of participants with MR or better. |
| Cohorts 1, 2, and 3: Duration of Response (DOR) as assessed by the IRC | Up to approximately 5 years | DOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first. |
| Cohorts 2 and 3: MRR as assessed by the IRC | Up to approximately 5 years | MRR is defined as the percentage of participants achieving PR or better. |
| Cohorts 1, 2, and 3: Progression-Free Survival (PFS) | Up to approximately 5 years | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the IRC and by the investigator. |
| Cohorts 1, 2, and 3: Time to major response as assessed by the IRC | Up to approximately 5 years | Time to major response is defined as the time from start of study treatment to the first documentation of major response. |
| All Cohorts: Time to major response as assessed by the investigator | Up to approximately 5 years | Time to major response is defined as the time from start of study treatment to the first documentation of major response. |
| Cohorts 1, 2, and 3: Overall Survival (OS) | Up to approximately 5 years | OS is defined as the time from first study drug administration to the date of death due to any cause. |
| Cohort 4: Time to next treatment | Up to approximately 5 years | Defined as the time from the start of treatment to the start of first subsequent therapy for WM. |
| Number of participants reporting adverse events | Up to approximately 5 years | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory abnormalities, physical examination results, and vital signs. |
| All Cohorts: Change from Baseline in Health-Related Quality of Life (HRQoL): NFLymSI-18 Disease-related Symptoms-Physical and Treatment-Related Side Effects Subscales | Baseline and approximately months 7, 13, 19, and 25 | HRQoL based on participant-reported outcomes using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Lymphoma Cancer Symptom Index - 18 Item (NFLymSI-18) Version 4. The questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and is divided into a total score. |
| All Cohorts: DOR as assessed by the investigator | Up to approximately 5 years | DOR is defined as the time from first determination of response until first documentation of progression or death, whichever occurs first. |
Countries
Australia, Canada, China, France, Greece, Italy, Spain, United Kingdom, United States
Outcome results
None listed