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).

Phase 2RecruitingNCT07638683

Shanghai Zhongshan Hospital30 enrolled

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma AL Amyloidosis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

1-Year Progression-Free Survival (PFS) Rate

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.

Time frame: From the start of treatment to 1 year, or until disease progression or death, whichever occurs first

Secondary Outcomes

Hematologic Complete Response (Heme-CR) rate

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.

Time frame: Up to 24 cycles (approximately 2 years)

Very Good Partial Response or Better (≥VGPR) Rate

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.

Time frame: Up to 24 cycles (approximately 2 years)

Minimal Residual Disease (MRD) Negativity Rate

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.

Time frame: 6 months and 12 months, and up to 24 cycles (approximately 2 years)

Organ Response Rate

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 frame: Up to 24 cycles (approximately 2 years)

Time to First Response

Time from the start of treatment to the first documented PR or better response according to IMWG criteria.

Time frame: Up to 24 cycles (approximately 2 years)

Duration of Response

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

Time frame: Up to 3 years from study start

Median Progression-Free Survival

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

Time frame: Up to 3 years from study start

Time to Next Treatment

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

Time frame: Up to 3 years from study start

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

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.

Time frame: Through study completion, up to 12 months after the end of study treatment.

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

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts