Clinical trial NCT06649695: A Phase II Trial of Teclistamab in Participants With Previously Treated Immunoglobulin Light-chain (AL) Amyloidosis
Official title: A Phase II Trial of Teclistamab in Participants With Previously Treated Immunoglobulin Light-chain (AL) Amyloidosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: AL Amyloidosis
Keywords: teclistamab
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
Collaborators: name: Janssen Research & Development
First posted: 2024-10-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Hematologic Complete Response (CR) rate
timeFrame: baseline up to 3 cycles of treatment (approximately 3 months)
Secondary outcomes:
measure: Hematologic Overall Response Rate (ORR) rate
timeFrame: Baseline up to progression of disease or death (approximately 3,5 years)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: South Australia Health
city: Sydney
country: Australia
facility: Westmead Hospital
city: Limoges
country: France
facility: CHU Limoges
city: Paris
country: France
facility: Paris St Louis
city: Essen
country: Germany
facility: University Hospital Essen
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S Policlinico "San Matteo"
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: CHU Limoges
name: Murielle Roussel, MD
role: PRINCIPAL_INVESTIGATOR
References: