TECLISTAMAB for Amyloid light-chain amyloidosis

Inclusion criteria

• {"criterion_text":"- 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.\n- 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.\n- 3. Age ≥ 18 years.\n- 4. Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2.\n- 5. Mayo stage I–IIIA cardiac disease at Screening (see Appendix K for the definition of Mayo stages of cardiac disease).\n- 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.\n- 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.\n- 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).\n- 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

• {"criterion_text":"- 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.\n- 2. Isolated soft-tissue involvement.\n- 3. Presence of non-AL amyloidosis.\n- 4. Previous anti-BCMA targeted therapy (including, but not limited to, bispecifics).\n- 5. Intolerance to dexamethasone that would prohibit treatment with trial therapy.\n- 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.\n- 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.\n- 8. Mayo stage IIIB cardiac disease at Screening (see Appendix K for the definition of Mayo stage IIIB of cardiac disease)."}

Primary endpoints

• {"endpoint_text":"- The hematologic CR rate at the completion of 3 cycles (M3) of teclistamab, according to current criteria for response in AL amyloidosis.","definition_or_measurement_approach":"Hematologic CR rate measured at completion of 3 cycles (M3) according to current response criteria for AL amyloidosis."}

Secondary endpoints

• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Hematologic ORR = proportion achieving best hematologic response of PR or better assessed at M1, M3, M6 and every 3 months thereafter."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"VGPR rate = proportion achieving VGPR or better at M1, M3, M6 and every 3 months thereafter."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Duration measured from initial documentation of hematologic PR/VGPR/CR to first documented hematologic PD; censoring at last disease assessment if no progression."}
• {"endpoint_text":"- • 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","definition_or_measurement_approach":"Organ response rate = proportion of patients with organ response among those with corresponding organ involvement, assessed at M1, M3, M6 and every 3 months; heart and kidney depth of response per Table 16 criteria."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Time from C1D1 to first efficacy evaluation where patient meets criteria for hematologic PR, VGPR or CR; censoring at PD or last evaluable assessment if no response."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"hemPFS = time from C1D1 to first documentation of hematologic PD or death (any cause); censor at last disease assessment if alive and not progressed."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"MOD-PFS = time from C1D1 to hematologic PD, cardiac/renal failure manifestation, or death; censoring at last adequate assessment if alive and MOD-PFS-free."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"MOD-EFS = time from C1D1 to hematologic PD, cardiac/renal failure, initiation of subsequent therapy for amyloidosis, or death; censor at last adequate assessment if alive and MOD-EFS-free."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"TST = time from C1D1 to initiation of subsequent therapy; death due to PD without subsequent therapy counted as event; censoring for withdrawal, loss to follow-up or death due to non-PD."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"OS = time from C1D1 to death; censor at last known alive date for patients alive or with unknown vital status."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"Safety and tolerability evaluated by AE type, frequency, severity, relationship to treatment, and changes in vital signs and physical examinations."}
• {"endpoint_text":"- • 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.","definition_or_measurement_approach":"MRD negativity by NGF = proportion achieving negative MRD at completion of 3 cycles."}
• {"endpoint_text":"- • The changes in QoL using EORTC QLQ30, EQ-5D-5L, and SF-36v2.","definition_or_measurement_approach":"Quality of life changes assessed using EORTC QLQ-C30, EQ-5D-5L and SF-36v2 instruments."}

France

Earliest CTIS Part Ii Submission Date

14-02-2025

Latest Decision Or Authorization Date

22-04-2025

Processing Time Days

67

Number Of Sites

2

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

04-04-2025

Latest Decision Or Authorization Date

25-04-2025

Processing Time Days

21

Number Of Sites

3

Number Of Participants

8

Greece

Earliest CTIS Part Ii Submission Date

23-01-2025

Latest Decision Or Authorization Date

24-04-2025

Processing Time Days

91

Number Of Sites

1

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

28-03-2025

Latest Decision Or Authorization Date

23-04-2025

Processing Time Days

26

Number Of Sites

1

Number Of Participants

3

Netherlands

Earliest CTIS Part Ii Submission Date

14-04-2025

Latest Decision Or Authorization Date

24-04-2025

Processing Time Days

10

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

European Myeloma Network B.V.

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Contract research organisations

Name

Health Data Specialists Ireland Limited

Responsibilities

Multiple sponsor duties including contracts with investigators & payments and other study coordination responsibilities (codes listed in sponsor duties)

Name

Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.

Responsibilities

Contracts with investigators & payments and study conduct support (sponsor duties codes as listed)

Third parties

• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Packaging & Labelling, Distribution to the sites, receipt, storage and destruction","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Janssen Research And Development LLC","duties_or_roles":"Submission IMPD-Q","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Health Data Specialists Ireland Limited","duties_or_roles":"Multiple sponsor duties including contracts with the investigators & payments and roles represented by codes: 1,10,11,12,14,15,3,5,6,7,8,9 (see sponsor duties list); explicit: Contracts with the investigators & payments","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.","duties_or_roles":"Sponsor duties including codes 1,12,15 (Contracts with the investigators & payments), 3,6,7,8","organisation_type":"Pharmaceutical company"}

Co-sponsors

• Emn Trial Office S.r.l. Impresa Sociale