Diagnosis of amyloidosis
Subjects with known or suspected amyloidosis of any organ
Pts with primary systemic amyloidosis
Untreated biopsy proven AL amyloidosis
Patients with multi-organ involvement by amyloidosis or evidence of amyloidosis-related organ dysfunction
Patients with known amyloidosis (AL) subtype amyloidosis
Known amyloidosis (MM patients)
Patients with known AL subtype amyloidosis
Non-AL amyloidosis
Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis; exception: patients with amyloid heavy (AH) or mixed AL/AH type amyloidosis are potentially eligible
Central nervous system involvement with disease under study (myeloma), or concurrent AL amyloidosis or plasma cell leukemia
Primary amyloidosis (AL) or myeloma complicated by amyloidosis
One or more organs impacted by AL amyloidosis according to consensus guidelines
Known or suspected amyloidosis
Patients with primary systemic amyloidosis
Subject medically diagnosed with AL amyloidosis that has required chemotherapy or an autologous stem cell transplant based upon: AL amyloidosis confirmed by biopsy with immunohistochemical staining or proteomic identification of AL amyloid fibril type, in subjects with definite monoclonal gammopathy in whom causative mutations of all known relevant amyloidogenic genes have been excluded
Newly diagnosed AL amyloidosis based upon: AL amyloidosis confirmed by biopsy with immunohistochemical staining or proteomic identification of AL amyloid fibril type in subjects with definite monoclonal gammopathy in whom causative mutations of all known relevant amyloidogenic genes have been excluded
Fulfilment of diagnostic criteria for AL amyloidosis
Primary amyloidosis
Amyloidosis
Patients with non-secretory MM or known primary amyloidosis are not eligible
Diagnosis of amyloidosis
Primary amyloidosis (AL) or myeloma complicated by amyloidosis
Presence of primary or associated amyloidosis (AL)
Biopsy-proven diagnosis of primary systemic light chain amyloidosis (AL amyloidosis) according to the following standard criteria:
Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis.
Primary amyloidosis
Primary AL (immunoglobulin light-chain) amyloidosis and myeloma complicated by amyloidosis
Patients with non-secretory MM or known amyloidosis are not eligible
Amyloidosis
Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis
History of or current amyloidosis
Non-AL amyloidosis
Subjects with known or likely systemic amyloidosis
No primary amyloidosis
Amyloidosis
Subjects with known or likely systemic amyloidosis
Subjects with known or suspected amyloidosis of any organ
Diagnosis of systemic AL amyloidosis (subjects with non-AL amyloidosis are not eligible);
Received at least one prior systemic therapy, which may include stem cell transplant, for AL amyloidosis;
Secondary or familial amyloidosis;
Primary amyloidosis
Any form of secondary / familial amyloidosis
Amyloidosis
Newly diagnosed, AL amyloidosis treatment naïve
Confirmed diagnosis of AL amyloidosis
Non-AL amyloidosis
Confirmed diagnosis of systemic AL amyloidosis
Non-AL amyloidosis
Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
Primary amyloidosis (amyloidosis associated with multiple myeloma is allowed).
Patients with known amyloidosis
Patients with known amyloidosis
Known amyloidosis
Light-chain (AL) amyloidosis; patients with secondary amyloidosis due to MM are eligible
Patients with primary systemic amyloidosis.
Patients with known amyloidosis.
Primary AL amyloidosis
Primary AL amyloidosis
Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.
Receiving any other investigational agent which would be considered as a treatment for AL amyloidosis
Amyloidosis
Patients must have a diagnosis of biopsy-proven diagnosis of AL amyloidosis according to the following standard criteria:\r\n* Histochemical diagnosis of AL amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence and immunohistochemistry\r\n* If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary\r\n* Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non amyloid forming [uninvolved] free light chain [FLC]) ? 50 mg/L)\r\n* Systemic amyloid organ involvement including renal, cardiac, gastrointestinal (GI) and/or nervous system involvement as well as soft tissue disease
Known amyloid involvement
COHORT B: biopsy proven light chain amyloidosis with organ involvement requiring therapy
Non-secretory MM or known amyloid light-chain (AL) amyloidosis
Biopsy-proven histochemical diagnosis of amyloid light-chain (AL) amyloidosis based on tissue specimens with Congo red staining or other histologic stain; thioflavin T or S, or crystal violet; tandem mass spec or immunohistochemistry (IHC) confirmation of immunoglobulin-derived amyloidosis is encouraged; cases in which histochemical confirmation is lacking need to be discussed with one of the Multiple Myeloma Research Foundation (MMRF) protocol chair/co-chairs
Measurable hematologic disease as defined by:\r\n* Serum differential free light chain concentration (dFLC, difference between amyloid forming [involved] and non-amyloid forming [uninvolved] free light chain [FLC]) >= 50 mg/L)
Measurable disease of amyloid light-chain (AL) amyloidosis as defined by at least one of the following:
Non-secretory MM or known amyloid light-chain (AL) amyloidosis
Light chain (AL) amyloidosis patients with Mayo cardiac stage III (defined as N-terminal proB-type natriuretic peptide measurement [proBNP] > 332 ng/L and cardiac troponin [cTnT] > 0.035 ug/L)
Systemic amyloid light chain amyloidosis
If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary.
Objective, measurable major (cardiac or renal) organ amyloid involvement as defined as follows (amyloid involvement of at least 1 required):
Primary systemic AL (immunoglobulin light chain) amyloidosis
Patients who have not been treated or who have received chemotherapy within 6 months, or SCT within 12 months, for the light-chain producing hematologic disease causing AL amyloidosis, at the time of the first dose of NEOD001 (month 1 day 1)
Known amyloid involvement
Patients must have a confirmed diagnosis of amyloid light-chain (AL) amyloidosis based on accepted clinical and laboratory criteria
Demonstrated clonal population of plasma cells in the bone marrow or positive immunohistochemical stain with anti-light chain anti-sera of amyloid fibrils
Primary systemic amyloid light (AL) chain amyloidosis (a build-up of amyloid light chain proteins in the blood)
Histopathology of amyloidosis or light chain deposition disease based on detection by polarizing microscopy of green bi-refringent material in Congo red-stained tissue specimens or characteristic electron microscopy appearance or immunohistochemical stain with anti-light chain anti-sera
Presence of primary (light chain) amyloidosis.
Histologically-proven AL amyloidosis, confirmed by positive Congo red stain with green birefringence on polarized light microscopy with evidence of measurable clonal disease that requires active treatment as defined below:
Documented active systemic amyloid light chain amyloidosis.
Primary systemic amyloid light-chain (AL) (immunoglobulin light chain) amyloidosis
Documented systemic light chain amyloidosis.