A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL).

Official title

A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL)

Overview

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

• Drug Teclistamab
  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 i

Primary outcome measures

• 1-Year Progression-Free Survival (PFS) Rate [Time frame: From the start of treatment to 1 year, or until disease progression or death, whichever occurs first]

Secondary outcome measures (9)

• Hematologic Complete Response (Heme-CR) rate [Time frame: Up to 24 cycles (approximately 2 years)]
• Very Good Partial Response or Better (≥VGPR) Rate [Time frame: Up to 24 cycles (approximately 2 years)]
• Minimal Residual Disease (MRD) Negativity Rate [Time frame: 6 months and 12 months, and up to 24 cycles (approximately 2 years)]
• Organ Response Rate [Time frame: Up to 24 cycles (approximately 2 years)]
• Time to First Response [Time frame: Up to 24 cycles (approximately 2 years)]
• Duration of Response [Time frame: Up to 3 years from study start]
• Median Progression-Free Survival [Time frame: Up to 3 years from study start]
• Time to Next Treatment [Time frame: Up to 3 years from study start]
• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time frame: Through study completion, up to 12 months after the end of study treatment.]

Eligibility criteria

Inclusion criteria

• Age ≥18 years, any sex/gender
• Diagnosis of multiple myeloma according to IMWG criteria
• Histopathologic diagnosis of AL amyloidosis confirmed by:

• Green birefringence under polarized light microscopy with Congo red staining; AND at least one of the following:

• Immunohistochemistry and/or immunofluorescence
• Mass spectrometry
• Electron microscopy/immunoelectron microscopy
• Measurable disease at screening
• Newly diagnosed, no prior anti-plasma cell therapy
• 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
• Male and female participants of childbearing potential must use at least 2 effective contraceptive methods during the study
• Voluntarily signed informed consent form (ICF)

Exclusion criteria

• Prior anti-myeloma therapy or stem cell transplantation
• 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
• Active infection or autoimmune disease
• Uncontrolled diabetes, hypertension, or other comorbidities
• Pregnant or lactating female
• Currently participating in another interventional study
• Any other condition that the investigator considers unsuitable for study participation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan Hospital Fudan University — Shanghai

Identifiers

NCT: NCT07638683 · SHZS-MMAL-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗