AL amyloidosis
Conditions
Interventions
Test group:BCMA/CD3 dual antibody therapy (CM336)
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Provide informed consent form; 2. Male or female patients aged 18 years or older; 3. Biopsy-proven diagnosis of AL amyloidosis, according to the following standard criteria: - Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence - If clinical and laboratory parameters are insufficient to establish AL amyloidosis, or in cases of doubt, amyloid typing may be necessary; 4. Measurable disease, as defined by serum differential free light-chain concentration (dFLC; defined as the difference between amyloid forming [involved] and nonamyloid forming [uninvolved] free light-chain [FLC]) =50 mg/L); 5. Received at least one prior line of therapy - Must have been exposed to CD38 mAb; 6. Relapsed/refractory AL amyloidosis or newly diagnosed AL amyloidosis with insufficient depth of hematologic response after induction therapy - Relapsed is defined as documented progressive disease >60 days after the last dose of prior therapy - Refractory is defined as the documented absence of a hematologic response or hematologic progression on or within 60 days after the last dose of prior therapy - Insufficient depth of hematologic response is defined as less than hematological PR by 2 cycles or less than hematologic VGPR by 4 cycles; 7. Eastern Cooperative Oncology Group performance status 80% unconjugated bilirubin and total bilirubin =30 mL/min; 11. Baseline oxygen saturation >92% in room air; 12. Absolute neutrophil count >=1000/µL - Platelet count >=75,000/µL - Hemoglobin >=85g/L; 13. Patients receiving hematopoietic growth factor support, including erythropoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and platelet agonists (e.g., eltrombopag, TPO, interleukin-11), must have a 2-week interval between growth factor support and screening evaluation. 14. The woman is not breastfeeding, is not pregnant, and agrees not to be pregnant during the study period and for the following 12 months. 15. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter. 16. Male patients must agree not to donate sperm from the initial screening period until 90 days after the last dose of medication; 17. Patients must voluntarily participate and be able to complete the study procedures and follow-up examinations;
Exclusion criteria
Exclusion criteria: 1. Non-AL amyloidosis, including hereditary amyloidosis; 2. Diagnosed with multiple myeloma, according to the International Myeloma Working Group criteria; 3. Have been exposed to BCMA-targeted treatment; 4. Known intolerance, hypersensitivity, or contraindication to BCMA BiTE cellular products; 5. Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathy greater than grade 2 with pain at baseline, regardless of whether they were currently receiving medical therapy, after excluding AL amyloidosis-related peripheral neuropathy; 6. Known intolerance, allergy, or contraindication to the active ingredients of BCMA/CD3 bispecific antibodies. 7. Staging at screening will be performed according to the Mayo 2004 staging, revised Mayo 2004 staging, and Mayo 2012 staging, based on the criteria outlined in the Diagnosis and Treatment Guidelines for Primary Light Chain Amyloidosis (2021 Revision); 8. Medically documented cardiac syncope, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease; 9. Ongoing or active infection, known HIV-positive status, or active hepatitis B or C infection; 10. Women who are pregnant or breastfeeding; 11. Any active gastrointestinal dysfunction that affects the patient's ability to swallow tablets or any active gastrointestinal dysfunction that may impact the absorption of the study medication. 12. Subjects had major surgery within 2 weeks before randomization (for example, general anesthesia), or have not fully recovered from the surgery, or surgery is arranged during the study period; 13. Receipt of a live attenuated vaccine within 4 weeks prior to the first dose of study medication; 14. According to the researcher's judgment, any condition including but not limited to serious mental illness, medical illness, or other symptoms/conditions that may affect study treatment, compliance, or the capability of providing informed consent. Necessary medication or supportive therapy is contraindicated with study treatment. Any diseases or complications that may interfere with the study. Patients are not willing to or cannot comply with study scheme; 15. Contraindications to any required concomitant medication or supportive therapy; 16. Any disease or complication that may interfere with the study procedures. 17. The patient is unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events and serious adverse events;The rate of achieving VGPR or better hematologic response after 4 cycles of BCMA/CD3 bispecific antibody treatment; | — |
Secondary
| Measure | Time frame |
|---|---|
| Health-related quality of life assessment;progression free survival; | — |
Countries
China
Contacts
Public ContactAn Gang
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Outcome results
None listed