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

NCT ID: NCT04115956

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-06
• Study Completion Date: 2022-01-05

Brief 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.

The study was intended to be a Phase 1/2 trial but was early terminated and never moved forward to Phase 2.

Detailed Description

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.

The study was intended to be a Phase 1/2 trial but was early terminated and study never moved forward to Phase 2.

Conditions

AL Amyloidosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Melflufen and dexamethasone in combination

Intravenous infusion of melflufen Day 1 of 28 day cycles, in combination of dexamethasone on Days 1 and 2 of each 28-day cycle.

Group Type: EXPERIMENTAL

Melphalan-Flufenamide (Melflufen)

Intervention Type: DRUG

Treatment consist of i.v. melflufen on Day 1 of each 28-day cycle.

Dexamethasone

Intervention Type: DRUG

Dexamethasone 40 mg (20 mg at investigator's discretion) administered on Days 1 and 2 of each 28-day cycle.

Interventions

Melphalan-Flufenamide (Melflufen)

Treatment consist of i.v. melflufen on Day 1 of each 28-day cycle.

Intervention Type: DRUG

Dexamethasone

Dexamethasone 40 mg (20 mg at investigator's discretion) administered on Days 1 and 2 of each 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

Dexamethason JENAPHARM

Eligibility Criteria

Inclusion Criteria

• 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 involvement
• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

Oncopeptides AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giovanni Palladini, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital San Matteo in Pavia

Locations

Boston University Medical Center

Boston, Massachusetts, United States

Fakultní Nemocnice Ostrava

Ostrava - Poruba, , Czechia

Centre Hospitalier Universitaire de Limoges

Limoges, , France

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Alexandra General Hospital of Athens

Athens, , Greece

Hadassah University Hospital Ein Kerem

Jerusalem, , Israel

Oslo University Hospital - Rikshospitalet

Oslo, , Norway

Hospital Clinic de Barcelona

Barcelona, , Spain

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

United States; Czechia; France; Germany; Greece; Israel; Norway; Spain; United Kingdom

Other Identifiers

OP201

Identifier Type: -

Identifier Source: org_study_id