NCT07151690RecruitingPhase 2
A Single-arm Single-center Trial of BCMA/CD3 Bispecific Antibody Treatment for Newly Diagnosed Amyloidosis (AL-003)
Institute of Hematology & Blood Diseases Hospital, China1 site in 1 country21 target enrollmentStarted: September 4, 2025Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Rate of Hematologic Very Good Partial Response (VGPR) or Better
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •The patient is informed of and voluntarily signs the informed consent form (ICF).
- •Age ≥18 years, regardless of sex.
- •Confirmed diagnosis of primary light-chain (AL) amyloidosis, in accordance with the Guidelines for the Diagnosis and Treatment of Systemic Light-chain Amyloidosis (2021 Revision).
- •Measurable disease at screening, defined as:
- •Difference between involved and uninvolved free light chains (dFLC) ≥50 mg/L, or
- •Serum involved free light chain ≥50 mg/L with an abnormal κ:λ ratio.
- •ECOG performance status ≤
- •Adequate organ function within 3 days prior to the first dose of the investigational drug, meeting all of the following criteria:
- •i. Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L, with no granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) administration within 7 days, and no pegylated G-CSF administration within 14 days prior to testing; ii. Hemoglobin (Hb) ≥75 g/L, with no whole blood or red blood cell transfusion within 7 days prior to testing; iii. Platelet count ≥70 × 10⁹/L, with no whole blood transfusion, platelet transfusion, or thrombopoietin receptor agonist treatment within 7 days prior to testing; iv. Hepatic function: alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤3 × ULN, total bilirubin ≤2 × ULN (subjects with Gilbert's syndrome are eligible if direct bilirubin ≤2 × ULN); v. Coagulation: international normalized ratio (INR) or activated partial thromboplastin time (APTT) ≤1.5 × ULN; vi. Renal function: estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m², calculated using the CKD-EPI equation.
- •Male and female patients of childbearing potential, and their partners, must agree to use effective contraceptive methods deemed appropriate by the investigator throughout the treatment period and for at least 3 months thereafter.
- •Male patients must agree not to donate sperm from the screening period until 90 days after the last dose of the investigational drug.
- •The patient must be willing and able to comply with all study procedures and follow-up visits.
- •Women not of childbearing potential are eligible for enrollment. Women of childbearing potential must have a negative serum or urine β-hCG pregnancy test at screening.
- •A woman of childbearing potential is defined as a sexually mature woman who has not undergone surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) and has not been postmenopausal for at least 12 consecutive months for reasons other than medical treatment. Women using oral contraceptives or intrauterine devices are considered of childbearing potential. Male subjects (including those who have undergone vasectomy) must agree to use condoms during sexual intercourse with women of childbearing potential and must have no plans to father a child from the time of signing the ICF until 3 months after the last dose of study treatment.
Exclusion Criteria
- Not provided
Arms & Interventions
BsAbs-treatment group
Experimental
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.
Intervention: anti-BCMA/CD3 bispecific antibody (Drug)
Outcomes
Primary Outcomes
Rate of Hematologic Very Good Partial Response (VGPR) or Better
Time Frame: 4 months
Proportion of participants achieving a hematologic response of VGPR or better (≥VGPR) 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)
Time Frame: 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 Outcomes
- 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.)
- 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.)
- Progression-Free Survival (PFS)(From the first dose to progression from any cause, up to approximately 36 months.)
- Minimal Residual Disease (MRD) Negativity Rate(From baseline to 24 months, assessed at predefined response evaluation time points.)
- Organ Response(12 months)
- 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.)
- 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.)
- Overall Response Rate (ORR)(The overall response rate (ORR) was evaluated at the end of cycle 4, 6, and 12 (28 days per cycle).)
- 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.)
Investigators
Study Sites (1)
Loading locations...
Similar Trials
Not yet recruiting
Phase 2
BCMA/CD3 BsAb Therapy for POEMS SyndromePOEMS SyndromeNCT07115654Institute of Hematology & Blood Diseases Hospital, China10
Not yet recruiting
Not Applicable
BCMA/CD3 BiTE for RRAL or NDAL Amyloidosis With Insufficient Depth of Hematologic Response After Induction TherapyAL AmyloidosisNCT06769555Institute of Hematology & Blood Diseases Hospital, China20
Recruiting
Not Applicable
BCMA/CD3 BsAb in the Treatment of High-risk Smoldering Multiple MyelomaHigh Risk Smoldering Multiple MyelomaNCT06745687Institute of Hematology & Blood Diseases Hospital, China20
Not yet recruiting
Phase 1
A Study of Fully Human BCMA CAR-T (CT103A) in Patients With Newly Diagnosed High-risk Multiple Myeloma (FUMANBA-2)Multiple MyelomaNCT05181501Nanjing IASO Biotechnology Co., Ltd.20
Recruiting
Phase 3
Study of BiRd Regimen Combined With BCMA CAR T-cell Therapy in Newly Diagnosed Multiple Myeloma (MM) PatientsMultiple MyelomaNCT04287660The First Affiliated Hospital of Soochow University20