A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis

• Status: Active, not recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oncopeptides AB
• Collaborator: PRA Health Sciences
• Treatments: BB 1101; Dexamethasone; Dexamethasone acetate; Melphalan

Criteria

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