Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The goal of this study is to evaluate the efficacy and safety of Sonrotoclax combined Regimen in patients with t(11;14) AL amyloidosis. Participants will receive the Sonrotoclax Plus Dexamethasone regimen with or without Daratumumab for 12 cycles. The Hematologic Response, Organ Response, Survival, and Safety will be evaluated.
Treatment options for AL amyloidosis are limited. Before the approval of daratumumab, newly diagnosed light-chain amyloidosis was often managed with anti-myeloma regimens such as bortezomib. For patients with relapsed/refractory (R/R) disease, there is currently a lack of standard treatment options both domestically and internationally. Guidelines recommend enrollment in clinical trials or the use of regimens containing previously unexposed agents, such as bortezomib or daratumumab.
Based on preliminary data of BCL-2 inhibitors in t(11;14) amyloidosis, this study aims to explore the efficacy and safety of sonrotoclax and dexamethasone with or without Daratumumab. Newly diagnosed patients with t（11;14）will receive the combination of sonrotoclax, daratumumab, and dexamethasone. t(11;14) Patients with relapsed/refractory AL amyloidosis (RRAL) will be treated with sonrotoclax plus dexamethasone. For transplant-eligible patients, stem cell collection is permitted during the induction phase of therapy. The timing of ASCT may be assessed after the primary endpoint evaluation (completion of 4 treatment cycles) and determined by the investigator.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sond±D | Experimental | Cohort A: sonrotoclax combined with daratumumab and dexamethasone in t(11;14) AL amyloidosis, newly diagnosed or previously untreated with anti-CD38 mAb therapy. Cohort B: sonrotoclax combined with daratumumab and dexamethasone in t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sonrotoclax | Drug | t(11;14) AL amyloidosis Newly diagnosed or previously untreated with anti-CD38 mAb therapy Induction therapy (C1-4) Sonrotoclax once daily ( dose depends on the 3+3 study design during safety run-in period in C1) Consolidation therapy (C5-12) Sonrotoclax once daily (same as the target dose in induction therapy) t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy Induction therapy (C1-4) Sonrotoclax once daily (dose depends on the 3+3 study design during safety run-in period in C1) Consolidation therapy (C5-12) Sonrotoclax once daily (same as the target dose in induction therapy) |
| Measure | Description | Time Frame |
|---|---|---|
| Best hematological ≥VGPR rate within four cycles of therapy | Defined as the proportion of patients achieving VGPR, or CR within four cycles of therapy | At the end of Cycle 4 (each cycle is 28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Hematological ORR after four cycles of therapy | Defined as the proportion of patients achieving PR,VGPR, or CR at the end of four cycles of therapy | At the end of Cycle 4 (each cycle is 28 days) |
| Hematological CR rate at the end of four cycles of therapy |
| Measure | Description | Time Frame |
|---|---|---|
| MRD negativity rate in patients achieving hematological CR | Defined as the MRD negativity rate in patients achieving hematological CR | 1 year |
| MRD negativity rate | Defined as the proportion of patients achieving MRD negativity |
Inclusion Criteria:
Patients who meet the diagnostic criteria for Primary Systemic Light Chain Amyloidosis (according to the Systemic Light Chain Amyloidosis Diagnosis and Treatment Guidelines (2021 Revision)).
Age ≥ 18 years.
Confirmed FISH test result of t(11;14) positive by each center or a third-party laboratory, or a prior FISH test report indicating t(11;14) positivity
ECOG Performance Status score of 0-2.
Presence of measurable disease, defined by at least one of the following criteria:
Adequate organ function, defined as:
Life expectancy greater than 6 months.
Patient understands and voluntarily signs an informed consent form (ICF).
Cohort Assignment:
Exclusion Criteria:
Meets the diagnostic criteria for active multiple myeloma or active lymphoplasmacytic lymphoma
Presence of other malignancies at an advanced stage with systemic metastases.
IgM-type AL amyloidosis.
Prior treatment with a BCL-2 inhibitor (BCL-2i).
Presence of any of the following severe cardiovascular diseases
Severe or persistent infection that is not effectively controlled. (Acute infection requiring antibacterial, antifungal, or antiviral therapy that has not resolved within 14 days prior to dosing).
Positive status for human immunodeficiency virus (HIV) antibody (HIVAb).
Serological status reflecting active viral hepatitis B (HBV) or hepatitis C (HCV) infection, as follows:
Patients receiving renal replacement therapy.
Patients with known hypersensitivity to any component of the investigational regimen.
Any condition that, in the investigator's judgment, would increase the risk to the subject or affect the study results.
Patients with AL amyloidosis currently participating in other investigational drug clinical studies.
Patients who are pregnant, breastfeeding, or planning to become pregnant during the study participation.
Patients who are receiving any moderate or strong CYP3A4 inhibitors (within ≤7 days or 5 half-lives, whichever is shorter) or strong CYP3A4 inducers (within ≤14 days or 5 half-lives, whichever is shorter) prior to the first dose of the study drug; or patients who require continuous treatment with moderate or strong CYP3A inhibitors or strong CYP3A inducers
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000075363 | Immunoglobulin Light-chain Amyloidosis |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D000686 | Amyloidosis |
Not provided
Not provided
| ID | Term |
|---|---|
| C556306 | daratumumab |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Daratumumab | Drug | t(11;14) AL patients insensitive to or relapsed after anti-CD38 mAb therapy Daratumumab (16 mg/kg intravenously or 1800 mg subcutaneously, once weekly C1-2; every two weeks C3-6; every month C7-12) |
|
| Dexamethasone | Drug | Dexamethasone (40 mg, once weekly) for 12 cycles. The dose was halved for patients 75 years of age or older, and in patients who were intolerant of dexamethasone, as judged by the investigators. |
|
Defined as the proportion of patients achieving CR at the end of four cycles of therapy |
| at the end of 4 cycles of therapy (each cycle is 28 days) |
| Cardiac response rate at the end of 6 cycles of treatment | Defined as the proportion of patients achieving Cardiac response at the end of 6 cycles of therapy | At the end of Cycle 6 (each cycle is 28 days) |
| Hepatic response rate at the end of 6 cycles of treatment | Defined as the proportion of patients achieving Hepatic response at the end of 6 cycles of therapy | At the end of Cycle 6 (each cycle is 28 days) |
| Renal response rate at the end of 6 cycles of treatment | Defined as the proportion of patients achieving Hepatic response at the end of 6 cycles of therapy | At the end of 6 cycles of treatment (each cycle is 28 days) |
| 1-year MOD-PFS rate | Defined as the proportion of patients in the safety analysis set who have not experienced a MOD-PFS event within 1 year after treatment. MOD-PFS is defined as the time from treatment initiation to the occurrence of any of the following events (whichever comes first): end-stage heart disease (requiring heart transplantation, left ventricular assist device, or intra-aortic balloon pump), end-stage renal disease (requiring dialysis or renal transplantation), hematological progression, or death | 1 year |
| 1-year PFS rate | Defined as the proportion of patients in the safety analysis set who are alive and free from hematological progression at 1 year after treatment. PFS is defined as the time from treatment initiation to hematological progression or death (whichever occurs first) | 1 year |
| 1-year OS rate | Defined as the proportion of patients in the safety analysis set who are alive at 1 year after treatment | 1 year |
| Time to Response (TTR) | Defined as the time from treatment initiation to the first hematological efficacy assessment achieving PR. | 1 year |
| Time to VGPR | Defined as the time from treatment initiation to the first hematological efficacy assessment achieving VGPR | 1 year |
| Time to Cardiac Response | Defined as the time from treatment initiation to the first cardiac efficacy assessment achieving response. | 1 year |
| Time to Renal Response | Defined as the time from treatment initiation to the first renal efficacy assessment achieving response | 1 year |
| Time to Hepatic Response | Defined as the time from treatment initiation to the first hepatic efficacy assessment achieving response. | 1 year |
| Adverse Events (AEs), Serious Adverse Events (SAEs), and laboratory abnormalities | the proportion of patients with Adverse Events (AEs), Serious Adverse Events (SAEs), and laboratory abnormalities after therapy | 1 year |
| Correlation analysis between different MRD satus groups and MOD-PFS, PFS and OS | Correlation analysis between different MRD satus groups and 1-year MOD-PFS, 1-year PFS and 1-year OS | 1 year |
| At the end of Cycle 9-12 (each cycle is 28 days) |
| D057165 |
| Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D010265 | Paraproteinemias |
| D000072473 |
| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |