AL Amyloidosis
Conditions
Keywords
teclistamab
Brief summary
This is a multicenter open-label, phase 2 study in participant with previously treated immunoglobulin light-chain (AL) Amyloidosis to evaluate the benefit of teclistamab
Interventions
DRUGTeclistamab
Teclistamab will be administered via a subcutaneous injection (SC)
Sponsors
European Myeloma Network B.V.
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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. * Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2 * Mayo stage I-IIIA cardiac disease at Screening * 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. However, patients who have received high-dose therapy with melphalan as their only therapy are also eligible. * 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. * Adequate bone marrow function, without transfusion or growth factors within 5 days prior to the first drug intake (C1D1), defined as: * Absolute neutrophils ≥1,000/mm3, * Platelets ≥75,000/mm3, * Hemoglobin ≥8.5 g/dL. * Adequate organ function, defined as: * Serum creatinine clearance (CKD-EPI formula) ≥20 mL/min, * Serum SGPT/ALT \<5.0 x Upper Limit of Normal (ULN), * Serum total bilirubin \<2.0 mg/dL or direct bilirubin ≤30% of the total, unless the patient has Gilbert's syndrome, where direct bilirubin should then be \<2.0 mg/dL, * Serum albumin ≥\<2.5 gr/dl (medication to correct serum albumin levels is permitted).
Exclusion criteria
* 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. * Isolated soft-tissue involvement. * Presence of non-AL amyloidosis. * Previous anti-BCMA targeted therapy (including, but not limited to, bispecifics). * Intolerance to dexamethasone that would prohibit treatment with trial therapy. * 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. * 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. * Mayo stage IIIB cardiac disease at Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Complete Response (CR) rate | baseline up to 3 cycles of treatment (approximately 3 months) | Percentage of participants achieving CR or better according to EHA/ISA guidelines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Overall Response Rate (ORR) rate | Baseline up to progression of disease or death (approximately 3,5 years) | Percentage of participants achieving Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) or better according to EHA/ISA guidelines |
Countries
Australia, France, Germany, Greece, Italy, Netherlands
Contacts
PRINCIPAL_INVESTIGATORMurielle Roussel, MD
CHU Limoges
Outcome results
None listed