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NCT Number: NCT07638683

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).

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

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Key information

Conditions

Multiple Myeloma AL Amyloidosis Amyloidosis Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoglobulin Light-chain Amyloidosis Immunoproliferative Disorders Lymphoproliferative Disorders Metabolic Diseases Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Nutritional and Metabolic Diseases Paraproteinemias Proteostasis Deficiencies Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Teclistamab

Drug

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.

Other names: Daratumumab

Primary outcomes

  1. 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

    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 outcomes

  1. Hematologic Complete Response (Heme-CR) rate

    Time frame: 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.

  2. Very Good Partial Response or Better (≥VGPR) Rate

    Time frame: 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.

  3. Minimal Residual Disease (MRD) Negativity Rate

    Time frame: 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.

  4. Organ Response Rate

    Time frame: 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).

  5. Time to First Response

    Time frame: 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.

  6. Duration of Response

    Time frame: Up to 3 years from study start

    Time from the start of treatment to death from any cause.

  7. Median Progression-Free Survival

    Time frame: Up to 3 years from study start

    Time from the start of treatment to disease progression or death from any cause, whichever occurs first.

  8. Time to Next Treatment

    Time frame: Up to 3 years from study start

    Time from the start of treatment to the initiation of first subsequent anti-myeloma therapy.

  9. 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.

    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.

Other outcomes

  1. Differential gene expression in bone marrow by RNA sequencing between baseline and disease progression in MM-AL patients.

    Time frame: Baseline and up to 3 years.

    Bone marrow transcriptome profiles will be analyzed by RNA sequencing at baseline and at disease progression to identify differentially expressed genes, altered signaling pathways, and molecular signatures predictive of disease progression in MM-AL patients. Data will be summarized as fold-change in gene expression, pathway enrichment scores, and predictive model performance metrics (e.g., AUC, sensitivity, specificity).

Study contacts

Contact information is provided by the study sponsor or research team.

Jing Li

CONTACT

[email protected]

+86-18149780650

Peng Liu

CONTACT

[email protected]

+86-021-64041990

Sponsors and collaborators

Lead sponsor

Shanghai Zhongshan Hospital

Other

Collaborators

  • Johnson & Johnson

Registry information

Official study 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)

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Jun 10, 2026
Registry last updated
Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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