AL Amyloidosis, Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, AL Amyloidosis, Teclistamab, Daratumumab
Brief summary
The goal of this clinical trial is to learn if teclistamab in combination with daratumumab (Tec-Dara) works to treat newly diagnosed multiple myeloma with concurrent light chain amyloidosis (MM+AL). It will also learn about the safety of this combination. The main questions it aims to answer are: Does Tec-Dara improve the 1-year progression-free survival rate compared to historical data (50% to 75%) in MM+AL patients? What are the rates of hematologic response (ORR, VGPR, CR, MRD negativity) and organ response in MM+AL patients treated with Tec-Dara? What medical problems do participants have when taking Tec-Dara? Participants will: Receive teclistamab subcutaneous injection with step-up dosing (0.06, 0.3, 1.5 mg/kg), followed by 1.5 mg/kg weekly in Cycle 1, 3.0 mg/kg every 2 weeks in Cycles 2-3, and 3.0 mg/kg every 4 weeks in Cycles 4-24 Receive daratumumab subcutaneous injection 1800 mg weekly in Cycles 1-2, every 2 weeks in Cycles 3-6, and every 4 weeks in Cycles 7-24 Continue treatment until disease progression, unacceptable toxicity, or a maximum of 24 cycles Undergo disease assessments every 28 days (±7 days) including laboratory tests for hematologic and organ response evaluation Provide bone marrow samples for MRD and RNA sequencing analysis
Interventions
DRUGTeclistamab
Teclistamab: A humanized IgG4-PAA bispecific antibody targeting BCMA and CD3. It bridges malignant plasma cells and CD3+ T cells, leading to T cell activation and perforin/granzyme-mediated lysis of BCMA+ tumor cells. Daratumumab: A humanized IgG1κ monoclonal antibody targeting CD38, which induces tumor cell lysis through complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. It also enhances T cell-mediated anti-myeloma immunity by increasing cytotoxic T helper cells and depleting CD38+ immunoregulatory cells, thereby potentiating teclistamab's activity.
Sponsors
Shanghai Zhongshan Hospital
Johnson & Johnson
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years, any sex/gender 2. Diagnosis of multiple myeloma according to IMWG criteria 3. Histopathologic diagnosis of AL amyloidosis confirmed by: * Green birefringence under polarized light microscopy with Congo red staining; AND at least one of the following: 1. Immunohistochemistry and/or immunofluorescence 2. Mass spectrometry 3. Electron microscopy/immunoelectron microscopy 4. Measurable disease at screening 5. Newly diagnosed, no prior anti-plasma cell therapy 6. Adequate laboratory values: * Hemoglobin ≥7.5 g/dL * Absolute neutrophil count ≥1.0×10⁹/L * Platelet count ≥70×10⁹/L (platelet transfusion acceptable; \>50×10⁹/L if ≥50% bone marrow nucleated cells are plasma cells) * ALT ≤2.5× upper limit of normal (ULN) * AST ≤2.5× ULN * Total bilirubin ≤2.0× ULN * Creatinine clearance ≥30 mL/min * Corrected serum calcium ≤14 mg/dL 7. Male and female participants of childbearing potential must use at least 2 effective contraceptive methods during the study 8. Voluntarily signed informed consent form (ICF)
Exclusion criteria
1. Prior anti-myeloma therapy or stem cell transplantation 2. Diagnosis of monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma, primary AL amyloidosis without concurrent MM, Waldenström macroglobulinemia, plasma cell leukemia, POEMS syndrome, or other malignancies within 3 years prior to enrollment 3. Active infection or autoimmune disease 4. Uncontrolled diabetes, hypertension, or other comorbidities 5. Pregnant or lactating female 6. Currently participating in another interventional study 7. Any other condition that the investigator considers unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-Year Progression-Free Survival (PFS) Rate | From the start of treatment to 1 year, or until disease progression or death, whichever occurs first | The percentage of participants who are alive and free from disease progression at 1 year after initiation of Tec-Dara treatment. Progression is defined according to IMWG criteria, including increase in serum M protein, urine M protein, or serum free light chain; development of new bone lesions or soft tissue plasmacytomas; or hypercalcemia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Complete Response (Heme-CR) rate | Up to 24 cycles (approximately 2 years) | Heme-CR will be defined as: involved free light-chain level less than the upper limit of the normal range with negative serum and urine immunofixation; normalization of the uninvolved free light-chain level or free light-chain ratio will not be required to determine a complete response. Heme-CR rate is the percentage of participants who achieve CR prior to subsequent anti-myeloma therapy, during or after the study treatment. |
| Very Good Partial Response or Better (≥VGPR) Rate | Up to 24 cycles (approximately 2 years) | Heme-VGPR is defined as a reduction in the dFLC to \<40 mg/L. ≥VGPR rate is the percentage of participants achieving VGPR and CR prior to subsequent anti-myeloma therapy during or after the study treatment. |
| Minimal Residual Disease (MRD) Negativity Rate | 6 months and 12 months, and up to 24 cycles (approximately 2 years) | Proportion of participants achieving MRD negativity at a sensitivity threshold of 10\^-5, assessed by next-generation flow cytometry (NGF) or next-generation sequencing (NGS). The MRD-negativity rate by 6 and 12 months will be reported descriptively. |
| Organ Response Rate | Up to 24 cycles (approximately 2 years) | Proportion of participants achieving organ response according to consensus criteria for AL amyloidosis, based on changes in NT-proBNP, cardiac troponin T/I, and estimated glomerular filtration rate (eGFR). |
| Time to First Response | Up to 24 cycles (approximately 2 years) | Time from the start of treatment to the first documented PR or better response according to IMWG criteria. |
| Duration of Response | Up to 3 years from study start | Time from the start of treatment to death from any cause. |
| Median Progression-Free Survival | Up to 3 years from study start | Time from the start of treatment to disease progression or death from any cause, whichever occurs first. |
| Time to Next Treatment | Up to 3 years from study start | Time from the start of treatment to the initiation of first subsequent anti-myeloma therapy. |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Through study completion, up to 12 months after the end of study treatment. | Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0. A participant with multiple adverse events of the same preferred term will be counted once. Adverse events will be summarized by frequency, severity (graded by CTCAE v5.0), and causality, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, hematologic toxicities, and infusion-related reactions. |
Countries
China
Contacts
CONTACTPeng Liu
CONTACTJing Li
PRINCIPAL_INVESTIGATORPeng Liu
Fudan University
Outcome results
None listed