A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis
A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis
This is a phase 1/2 open label study of melphalan flufenamide (melflufen) in combination with
 dexamethasone for participants with Al amyloidosis following at least one prior line of
 therapy. Melflufen will be administered on Day 1 of each 28-day cycle in combination with
 dexamethasone on days 1 and 2.

 In both phases, treatment of each individual participant will continue for up to 8 cycles or
 until any stopping events occur.

 Approximately 46 participants will be enrolled.
This is a clinical trial of melphalan flufenamide (melflufen), a peptide-conjugated alkylator
 which belongs to an novel class of drugs called peptidase-enhanced compounds, and targets the
 transformation process of tumor cells with a unique mechanism of action, as potential
 treatment option of AL amyloidosis.

 AL amyloidosis is a rare progressive disease caused by proteotoxic light chain protein
 produced by small plasma cell clone. This plasma cell dyscrasia is characterized by
 monoclonal plasma cell's excessive production of monoclonal immunoglobulin light-chains that
 tends to misfold and subsequently deposit as amyloid fibrils in visceral organs. The plasma
 cell dyscrasia in AL amyloidosis is similar to that in multiple myeloma (MM) and therapies
 that are effective in MM are often used to treat AL amyloidosis.

 Melphalan flufenamide is currently been evaluated in several ongoing clinical trials in
 patients with multiple myeloma, with observed efficacy. There are currently no therapies
 approved for treatment of AL amyloidosis and based on the efficacy of melphalan flufenamide
 and the demonstrated efficacy of melphalan (and other alkylators), it is anticipated that
 patients with AL amyloidosis may receive benefit from treatment with melphalan flufenamide.

 This study consist of a screening period (up to 28 days), a treatment period (up to 8 cycles)
 and a follow-up period (up to 24 months).

 Phase 1: Approximately 8-30 participants will be screened to achieve 7-23 enrolled
 participants.

 Phase 2: Approximately 30 participants will be screened to achieve 23 enrolled participants.
Inclusion Criteria: (For full list of inclusion criteria, see study protocol)

 -  Male or female, age 18 years or older at the time of signing the informed consent

 -  Proven histochemical diagnosis of AL amyloidosis based on tissue specimens with Congo
 red staining

 -  At least one prior line of therapy, defined as either one non-transplant regimen, one
 ASCT (autologous stem cell transplantation), or one regimen of induction therapy
 followed by a single ASCT. No more that 4 cycles of melphalan containing chemotherapy
 is allowed.

 -  Measurable hematologic disease

 -  Objectively measurable organ amyloid involvment

 -  ECOG performance status ≤ 2 (ECOG = Eastern cooperative oncology group)

 -  Women of child bearing potential must have a negative serum or urine pregnancy test

 -  Less than 30% plasma cells in bone marrow aspirate or biopsy

 -  Acceptable laboratory results met (absolute neutrophil count (ANC), platelet count,
 hemoglobin, total bilirubin,alkaline phosphatase, AST (aspartate aminotransferase) and
 ALT (alanine aminotransferase), renal function)

 -  Male participant agrees to use contraception during treatment and 90 days after last
 dose of melflufen

 Exclusion Criteria: (For full list of exclusion criteria, see study protocol)

 -  Amyloidosis due to known mutations of the transthyretin gene or presence of another
 non-AL amyloidosis

 -  Evidence of gastro-intestinal bleeding

 -  Cardiac risk stage 3

 -  Low platelets value with evidence of mucosal or internal bleeding

 -  Medical documented cardiac syncope, NYHA Class 3 or 4 congestive heart failure,
 myocardial infarction, unstable angina pectoris, clinically significant ventricular
 arrhythmias (NYHA=New York Heart Association Functional Classification)

 -  Clinically significant finding on 24 h Holter recording

 -  Severe orthostatic hypotension

 -  Clinically significant factor X deficiency

 -  Clinically significant autonomic disease

 -  Any medical condition that would impose excessive risk to the patient

 -  Serious psychiatric illness, active alcoholism or drug addiction that may hinder or
 confuse compliance

 -  Known HIV or active hepatitis B or C viral infections

 -  Previous cytotoxic therapies, including cytotoxic investigational agents within 3
 weeks prior to start of study treatment. Monoclonal antibodies within 4 weeks.
 Concomitant immunotherapy, investigational therapy and anticoagulation therapy are not
 permitted

 -  Prior autologous or allogenic stem cell transplant within 12 weeks of initiation of
 therapy

 -  Prior allogeneic stem cell transplant with active graft-host-disease

 -  Prior major surgical procedure or radiation therapy within 4 weeks of the first dose
 of study treatment