Teclistamab-Daratumumab in AL Amyloidosis

NCT07110844 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: AAAV88271452862
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate whether teclistamab-daratumumab combination is effective and safe in AL amyloidosis. The study treatment is divided into cycles (C) and each cycle is 28 days (D). Study treatment is expected to last 6 months.

Conditions

Amyloid Light-chain Amyloidosis

Keywords

Untreated AL Amyloidosis; untreated light chain amyloidosis; light chain amyloidosis; AL Amyloidosis

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months from treatment initiation

Secondary Outcomes (25)

• Minimal Residual Disease (MRD) negativity rate by Free Light Chain Mass Spectrometry (FLC-MS) in serum

  1 month, 3 months, 6 months, and 18 months

• MRD-negativity rate by multiparameter flow cytometry (MFC) in bone marrow

  6 months and 18 months

• Time to heme-CR

  Day 1 of each cycle, and every 6 weeks after treatment cessation (up to 1 year)

• Major organ deterioration-progression-free survival (MOD-PFS) rate

  From Cycle 2 to Cycle 6 Day 1 (Each cycle is 28 days), End of treatment visit (up to 6 months from treatment initiation), and up to 18 months from treatment initiation

• Overall survival rate

  Through study completion, up to 18 months from treatment initiation

Other Outcomes (7)

• Hematologic event-free survival (Heme-EFS)

  Throughout Cycle 2 and Cycle 6 (each cycle is 28 days) on Day 1; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months from treatment initiation)

• CD4 cell count

  Baseline until 18 months from treatment initiation

• CD8 cell count

  Baseline until 18 months from treatment initiation

Study Arms (1)

Teclistamab-Daratumumab

EXPERIMENTAL

All participants in this study will receive teclistamab and daratumumab.

Drug: Teclistamab; Drug: Daratumumab and Hyaluronidase-fihj

Interventions

Teclistamab DRUG

Teclistamab is a T-cell redirecting bispecific antibody (BsAb) targeting CD3 on T-cells and B-cell maturation antigen (BCMA) on plasma cells.

Also known as: TECVAYLI, teclistamab-cqyv

Teclistamab-Daratumumab

Daratumumab and Hyaluronidase-fihj DRUG

Daratumumab is an monoclonal antibody that targets the CD38 protein on the surface of myeloma cells.

Also known as: DARZALEX FASPRO, Daratumumab

Teclistamab-Daratumumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years and able to sign Informed Consent Form (ICF). If the individual being considered for participation in this study is unable to provide informed consent due to medical, cognitive, or other conditions, a legally authorized representative (LAR) may consent on their behalf.
• Ability to comply with the study protocol, in the investigator's judgment.
• Confirmed histopathological diagnosis of systemic AL amyloidosis by mass spectrometry or immunohistochemistry (IHC) or Immunofluorescence (IF) on a tissue biopsy that is positive for Congo Red.
• Patient must not have received any prior plasma cell clone-directed therapy.
• Measurable hematologic disease, defined as one of the following:
• Difference between involved and uninvolved serum free light chain (dFLC) ≥50 mg/L and/or 5 mg/dL
• Serum M-protein ≥0.5 g/dL on protein electrophoresis
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• One or more organs involved by AL amyloidosis as per consensus guidelines
• Pre-treatment clinical laboratory values meeting the following criteria during the screening phase:
• Absolute neutrophil count ≥0.75 × 10\^9/L
• Hemoglobin level ≥8.0 g/dL; red blood cell transfusion allowed until 7 days before C1D0.
• Platelet count ≥50 × 10\^9/L; Platelet transfusions are acceptable without restriction during the Screening period
• Alanine aminotransferase level (ALT) ≤2.5 times the Upper Limit of Normal (ULN)
• Aspartate aminotransferase (AST) ≤2.5 times the ULN

You may not qualify if:

• Prior therapy for AL amyloidosis or multiple myeloma with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to C1D0.
• Patients meeting criteria for symptomatic multiple myeloma by any one of the following: (a) Lytic lesions on imaging (Skeletal survey, whole body CT or MRI, or PET/CT) (b) Plasmacytoma, (c) Hypercalcemia without any alternate etiology, (d) Bone marrow plasma cell infiltrate of greater than 60%.
• Patients with involved/uninvolved serum FLC ratio\>100 as the sole myeloma-defining event will be allowed.
• Evidence of significant cardiovascular conditions as specified below:
• NT-Pro BNP \> 8500 pg/mL, and/or
• NYHA Class IIIb or IV functional class
• History of other malignancy that could affect compliance with the protocol or interpretation of results.
• Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer, or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment.
• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal).
• Patients on renal replacement therapy
• Patients with HIV who are not on HAART or those with active hepatitis A, B, or C infection.
• Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted, as per investigators' discretion.
• Known hypersensitivity to any of the agents
• Patients who are receiving any other investigational agent concurrently.

Sponsors & Collaborators

• Suzanne Lentzsch, MD: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Study Officials

• Suzanne Lentzsch, MD, PhD

  Columbia University

  STUDY CHAIR

Central Study Contacts

Central Nurse Navigator, RN

CONTACT

(212) 342 5162; cancerclinicaltrials@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and the Director of the Multiple Myeloma and Amyloidosis Program

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 8, 2025
• Study Start: November 7, 2025
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): October 1, 2033
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)