BCMA/CD3 Bispecific Antibody Treatment for Newly Diagnosed Amyloidosis
- Conditions
- Systemic Light Chain Amyloidosis
- Interventions
- Drug: anti-BCMA/CD3 bispecific antibody
- Registration Number
- NCT07151690
- Brief Summary
This is a prospective, single-arm, single-center clinical study designed to evaluate the efficacy and safety of low-dose BCMA/CD3 bispecific antibody (CM336) in patients newly diagnosed with systemic light chain (AL) amyloidosis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 10
1. Ability and willingness to provide written informed consent. 2. Age ≥18 years. 3. Diagnosed with primary systemic light chain (AL) amyloidosis based on 2021 Chinese diagnostic and treatment guidelines.
4. Measurable disease at screening: difference between involved and uninvolved serum free light chains (dFLC) >50 mg/L.
5. Newly diagnosed and treatment-naïve AL amyloidosis. 6. ECOG≤2. 7. Hematologic Function
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Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L, without granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support within 7 days prior to screening, and without pegfilgrastim within 14 days prior to screening.
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Hemoglobin ≥ 75 g/L, without whole blood or red blood cell transfusion within 7 days prior to screening.
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Platelet count ≥ 70 × 10⁹/L, without platelet transfusion or thrombopoietic growth factor treatment within 7 days prior to screening.
8. Hepatic Function Alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN); Aspartate aminotransferase (AST) ≤ 3 × ULN; Total bilirubin ≤ 2 × ULN (direct bilirubin ≤ 2.0 × ULN is allowed in patients with Gilbert's syndrome).
9. Coagulation Function International normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
10. Renal Function Estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m², measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Participants meeting any of the following criteria will be excluded:
- Non-AL amyloidosis (e.g., hereditary, other types).
- Diagnosis of symptomatic multiple myeloma according to the 2022 Chinese MM guidelines.
- Ineligible for anti-BCMA/CD3 therapy due to severe cardiopulmonary disease or other conditions.
- Any other reason that, in the investigator's judgment, makes the patient an inappropriate candidate for this treatment protocol.
- Receipt of a live vaccine or attenuated live vaccine within 4 weeks prior to the first administration of the investigational drug, or planned receipt of such vaccines during the study period.
- Major surgery requiring general anesthesia or major trauma within 4 weeks prior to the first administration of the investigational drug, or if major surgery is anticipated during the study period; subjects who are still in the postoperative/wound healing recovery period as assessed by the investigator will be considered unsuitable for study participation.
- Presence of autoimmune diseases or risk thereof (e.g., prior organ transplantation requiring immunosuppressive therapy). Exceptions include well-controlled type I diabetes mellitus, hypothyroidism managed with hormone replacement therapy, Graves' disease with normal thyroid function confirmed by clinical and laboratory assessment, and localized skin diseases (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment.
- Presence of significant cardiovascular or cerebrovascular disease, including:
- Occurrence of major cardiovascular or cerebrovascular events within 6 months prior to first dosing (e.g., unstable angina, myocardial infarction, transient ischemic attack, subarachnoid hemorrhage/intracranial hemorrhage, severe brain injury, stroke, seizure, deep vein thrombosis, pulmonary embolism).
- New York Heart Association (NYHA) class IV heart failure (see Appendix 7).
- Heart failure deemed by the investigator to be primarily due to ischemic cardiomyopathy (e.g., history of myocardial infarction with elevated troponin and ECG abnormalities, or confirmed by coronary artery disease), rather than mainly attributable to AL amyloidosis.
- For patients with amyloid-related heart failure, hospitalization for a cardiac event within 4 weeks prior to first dosing.
- Coronary artery bypass grafting or percutaneous coronary intervention with stent placement within 6 months prior to first dosing.
- History of sustained ventricular tachycardia or ventricular fibrillation, or atrioventricular (AV) conduction disease with sinus arrest (SA) requiring device therapy; patients with implanted pacemakers/ICDs are eligible, but those without implantation are excluded.
- Corrected QT interval (QTcF, calculated by Fridericia's formula) >500 msec. Patients with pacemakers or ICDs can be included regardless of QT correction formula results.
- Resting systolic blood pressure <90 mmHg.
- Other significant cardiovascular or cerebrovascular diseases deemed unsuitable for participation by the investigator.
9. Patients with interstitial lung disease or non-infectious pneumonitis (e.g., pneumoconiosis, radiation pneumonitis, drug-related pneumonitis) whose condition or history may interfere with evaluation/management of drug-related pulmonary toxicity, or those requiring supplemental oxygen for impaired lung function.
10. Receipt of oral anti-infective therapy within 2 weeks prior to first dosing, or systemic intravenous anti-infective therapy within 4 weeks prior to first dosing.
11. Active infections, including:
- Active hepatitis B infection [hepatitis B virus DNA (HBV-DNA) positive].
- Active hepatitis C infection or positive hepatitis C virus (HCV) antibody with detectable HCV-RNA.
- Human immunodeficiency virus (HIV) infection, confirmed by positive serology.
- Active or latent syphilis infection (Treponema pallidum antibody positive).
- Active pulmonary tuberculosis (diagnosed within 3 months prior to first dosing or during screening by chest imaging or other relevant assessments).
12. History of severe allergic reaction to monoclonal antibodies of human origin, or known hypersensitivity to any component of CM336.
13. Presence of other malignancies within 5 years prior to first dosing, except for adequately treated localized non-melanoma skin cancers, cervical carcinoma in situ, or ductal carcinoma in situ of the breast, provided no recurrence has occurred within 5 years.
14. Any condition that may interfere with compliance to the study protocol (e.g., substance abuse, epilepsy, psychiatric or cognitive disorders), any concurrent illness or treatment considered by the investigator to potentially confound study results or increase medical risk, or if the investigator judges that participation is not in the subject's best interest (e.g., risk of harm to health).
15. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women of childbearing potential must have a negative pregnancy test within 7 days prior to first dosing (see Appendix 8).
16. Women of childbearing potential (see Appendix 8) unwilling to use highly effective contraception during the study and for 6 months after the last administration of study drug; male subjects with female partners of childbearing potential unwilling to use highly effective contraception during the study and for 6 months after the last administration of study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BsAbs-treatment group anti-BCMA/CD3 bispecific antibody Treatment involves a 12-cycle course of weekly subcutaneous CM336, with step-up dosing during the first week (3 mg on Day 1, 20 mg on Day 4, and 40 mg weekly from Day 8 onward). Dose frequency may be reduced to every two weeks in patients achieving ≥VGPR after 4 cycles.
- Primary Outcome Measures
Name Time Method Rate of Hematologic Very Good Partial Response (VGPR) or Better From the start of treatment (Day 0), at the end of Cycle 4 (each cycle is 28 days), at the end of Cycle 8 (each cycle is 28 days), and at the end of Cycle 12 (each cycle is 28 days) Proportion of participants achieving a hematologic response of VGPR or better (≥VGPR) after 4 treatment cycles of anti-BCMA/CD3 bispecific antibody (CM336), assessed using consensus criteria for AL amyloidosis hematologic response.
Incidence and Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) From the first dose through 30 days after the last dose, up to approximately 24 months. Safety will be assessed by monitoring the incidence, nature, and severity of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs) such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), graded according to NCI CTCAE v5.0 and ASTCT criteria. Dose interruptions, modifications, or discontinuations due to toxicity will also be recorded.
- Secondary Outcome Measures
Name Time Method Time to First Hematologic Response (TTR) From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months. Best Hematologic Response Achieved From the first dose until the best hematologic response (≥PR) is achieved, assessed up to approximately 24 months. The deepest hematologic response (e.g., PR, VGPR, CR, or sCR) observed at any time during the treatment period.
Duration of Hematologic Response (DOR) From the date of first documented hematologic response to the date of disease progression or death, whichever occurs first, up to approximately 24 months. Time from the first documented hematologic response to disease progression or death, whichever occurs first.
Overall Response Rate (ORR) At the end of Cycle 4 (each cycle is 28 days), approximately 16 weeks from the first dose. Progression-Free Survival (PFS) From the first dose to progression from any cause, up to approximately 36 months. Overall Survival (OS) From the first dose to death from any cause, up to approximately 36 months. Minimal Residual Disease (MRD) Negativity Rate At the time of achieving hematologic complete response, up to approximately 24 months. Standardized uptake value (SUV) At baseline (prior to first dose), at the end of Cycle 4, Cycle 8, and Cycle 12 (each cycle = 28 days). Standardized uptake value (SUV) of 18F-92/AV45/TPZA/FT8, 11C-PIB for each target lesion of subject or suspected Pan-Amyloid related diseases.
Trial Locations
- Locations (1)
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
🇨🇳Tianjin, China
Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences🇨🇳Tianjin, China