A Trial of a novel agent in participants with previously treated Immunoglobulin Light-Chain (AL) Amyloidosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Myeloma Network B.V., Emn Trial Office S.r.l. Impresa Sociale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Jul 2025 → ongoing

Decision date (initial)

2025-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Janssen Research & Development, LLC

External identifiers

EU CT number

2024-519191-90-00

ClinicalTrials.gov

NCT06649695

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the hematologic CR rate after 3 cycles of single-agent teclistamab in patients with previously treated AL amyloidosis.

Secondary objectives 13

1. 1. To evaluate the hematologic ORR, defined as the proportion of patients achieving CR, VGPR, or PR.
2. 2. To evaluate the proportion of patients achieving at least VGPR (≥VGPR = CR + VGPR).
3. 3. To evaluate the duration of hematologic response.
4. 4. To evaluate the rate and depth (as applicable) of organ response (heart, renal, liver) according to standard criteria.
5. 5. To evaluate the time to hematologic response.
6. 6. To evaluate hematologic progression-free survival (hemPFS).
7. 7. To evaluate major organ deterioration progression-free survival (MOD-PFS).
8. 8. To evaluate major organ deterioration event-free Survival (MOD-EFS).
9. 9. To evaluate the time to subsequent therapy (TST).
10. 10. To evaluate OS
11. 11. To determine the safety and tolerability of teclistamab (type, frequency, severity, and relationship of adverse events to trial treatment).
12. 12. To assess MRD in the bone marrow by NGF after 3 cycles of single-agent teclistamab and at the end of treatment in patients with previously treated AL amyloidosis.
13. 13. To assess quality of life (QoL; EORTC QLQ-C30, EQ-5D-5L, SF-36v2).

Conditions and MedDRA coding

Immunoglobulin Light-Chain (AL) Amyloidosis

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. 1. Histologic diagnosis of AL amyloidosis and typed with immunohistochemistry/ immunofluorescence, immunoelectron microscopy, or mass spectrometry. In patients with biopsy-confirmed amyloidosis, ambiguous amyloid typing results, and cardiac involvement alone, a negative pyrophosphate (PYP) or technetium-99m (99mTc) and 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD-Tc99m) bone scan is required to distinguish cardiac involvement due to AL amyloidosis from amyloid transthyretin (ATTR) amyloidosis. Data from the initial diagnosis are accepted.
2. 2. Genetic testing must be negative for transthyretin mutations associated with hereditary amyloidosis, or immunohistochemistry/ immunofluorescence/ immunoelectron microscopy/ mass spectrometry of amyloid deposits must provide clear evidence of κ or λ light chains in patients who present with peripheral neuropathy or heart as the dominant organ involvement. Data from the initial diagnosis are accepted.
3. 3. Age ≥ 18 years.
4. 4. Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.
5. 5. Mayo stage I–IIIA cardiac disease at Screening (see Appendix K for the definition of Mayo stages of cardiac disease).
6. 6. Relapsed patients must have received at least 1 line of treatment, including Dara and bortezomib. Patients must have received at least two cycles of therapy.
7. 7. Measurable hematologic disease: a dFLC >20 mg/L with an abnormal κ/λ ratio (with Freelite® test kits, The Binding Site) or presence of a monoclonal spike ≥0.5 g/dL.
8. 8. At least one symptomatic organ involvement (heart, kidney, liver, gastrointestinal [GI] tract or peripheral nervous system) (see Appendix B for the definition of symptomatic organ involvement).
9. 9. A wash-out period of at least 14 days from the date of the last administration of any previous antitumor therapy or investigational treatment, meaning that the patient must not have received any treatment for AL amyloidosis for at least 14 days prior to Cycle 1 Day 1 (C1D1) of this trial.

Exclusion criteria 8

1. 1. Amyloid-specific syndrome, such as carpal tunnel syndrome or skin purpura, as the only evidence of disease. The finding of isolated vascular amyloid in a bone marrow biopsy specimen or in a plasmacytoma is not indicative of systemic amyloidosis.
2. 2. Isolated soft-tissue involvement.
3. 3. Presence of non-AL amyloidosis.
4. 4. Previous anti-BCMA targeted therapy (including, but not limited to, bispecifics).
5. 5. Intolerance to dexamethasone that would prohibit treatment with trial therapy.
6. 6. MM diagnosed as per the International Myeloma Working Group (IMWG) criteria, with the exception of monoclonal gammopathy of unknown significance (MGUS) or smoldering myeloma, not requiring treatment. Note: A MM diagnosis with a serum FLC ratio >100, as the only myeloma-defining event, does NOT constitute an exclusion.
7. 7. All hematologic malignancies, with the exception of low-risk Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms (MPNs) and low-risk myelodysplastic syndromes (MDS), not requiring treatment.
8. 8. Mayo stage IIIB cardiac disease at Screening (see Appendix K for the definition of Mayo stage IIIB of cardiac disease).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The hematologic CR rate at the completion of 3 cycles (M3) of teclistamab, according to current criteria for response in AL amyloidosis.

Secondary endpoints 13

1. • The hematologic ORR, defined as the proportion of patients achieving a best hematologic response of PR or better, at the completion of 1 (M1), 3 (M3), and 6 cycles (M6), and every 3 months thereafter.
2. • The VGPR rate, defined as the proportion of patients achieving a best hematologic response of VGPR or better, at the completion of 1 (M1), 3 (M3), and 6 cycles (M6), and every 3 months thereafter.
3. • The duration of hematologic response, defined as the time from the date of initial documentation of hematologic PR, VGPR, or CR, to the date of first documented evidence of hematologic progressive disease (PD). For patients who have not progressed, data will be censored at the last disease assessment.
4. • The rate of organ response according to standard criteria, defined as the proportion of patients achieving an organ response among patients with corresponding organ involvement, at the completion of 1 (M1), 3 (M3) and 6 cycles (M6), and every 3 months thereafter. For heart and kidney, the depth of response will be presented at the completion of 1 (M1), 3 (M3) and 6 cycles (M6), and every 3 months thereafter, based on the criteria mentioned on Table 16
5. • The time to hematologic response, defined as the time from the date of C1D1 to the date of the first efficacy evaluation during which the patient has met all criteria for hematologic PR, VGPR or CR. Patients without a hematologic response will be censored, either at the date of PD or, in the absence of PD, at the last evaluable disease assessment.
6. • The hemPFS, defined as the time from the date of C1D1 to the date of first documentation of hematologic PD, or death due to any cause, whichever occurs first. Patients who are still alive and not yet progressed will be censored at the last disease assessment.
7. • The MOD-PFS, defined as the time from the date of C1D1 to hematologic PD, manifestation of cardiac/renal failure, or death, whichever occurs first. For alive and MOD-PFS-free patients, censoring will be considered at the last adequate disease assessment.
8. • The MOD-EFS, defined as the time from the date of C1D1 to hematologic PD, manifestation of cardiac/renal failure, initiation of subsequent therapy for amyloidosis, or death, whichever occurs first. For alive and MOD-EFS-free patients, censoring will be considered at the last adequate disease assessment.
9. • The TST, defined as the time from the date of C1D1 to the date of initiation of subsequent therapy. Death due to PD (including cardiac/renal failure as per MOD-PFS definition) without the start of subsequent therapy will be considered as an event. Patients who withdrew trial consent, were lost to follow-up or died due to causes other than PD, will be censored at the date of death or at the date last known to be alive.
10. • The OS, defined as the time from the date of C1D1 to the date of patient’s death. Patients who are alive or with unknown vital status will be censored at the date last known to be alive.
11. • The safety and tolerability of teclistamab, by type, frequency, severity, relationship of adverse events to trial treatment, and changes in vital signs and physical exams.
12. • The MRD negativity rate by NGF, defined as the proportion of patients achieving negative MRD at the completion of 3 cycles of treatment with Teclistamab.
13. • The changes in QoL using EORTC QLQ30, EQ-5D-5L, and SF-36v2.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Myeloma Network B.V.

Sponsor organisation

European Myeloma Network B.V.

Address

Blaak 555

City

Rotterdam

Postcode

3011 GB

Country

Netherlands

Scientific contact point

Organisation

European Myeloma Network B.V.

Contact name

Dr. Murielle Roussel

Public contact point

Organisation

European Myeloma Network B.V.

Contact name

Prof. Pieter Sonneveld

Third parties 4

Emn Trial Office S.r.l. Impresa Sociale

Sponsor organisation

Emn Trial Office S.r.l. Impresa Sociale

Address

Via Saluzzo 1/a, TO

City

Turin

Postcode

10125

Country

Italy

Scientific contact point

Organisation

Emn Trial Office S.r.l. Impresa Sociale

Contact name

Prof. Mario Boccadoro

Public contact point

Organisation

Emn Trial Office S.r.l. Impresa Sociale

Contact name

Prof. Mario Boccadoro

Sponsor responsibilities

Article 77 compliance

European Myeloma Network B.V.

Contact point sponsor

European Myeloma Network B.V.

Article 77 implementation

European Myeloma Network B.V.

Locations

5 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications