World Health Organization site
Skip Navigation Links

Main
Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT04115956
Date of registration: 29/08/2019
Prospective Registration: Yes
Primary sponsor: Oncopeptides AB
Public title: A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis
Scientific title: An Open-Label, Phase 1/2 Study of Melflufen and Dexamethasone for Patients With AL Amyloidosis Following at Least One Prior Line of Therapy
Date of first enrolment: August 6, 2020
Target sample size: 46
Recruitment status: Recruiting
URL:  https://clinicaltrials.gov/show/NCT04115956
Study type:  Interventional
Study design:  Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).  
Phase:  Phase 1/Phase 2
Countries of recruitment
Czechia France Germany Greece Israel Italy Norway Poland
Spain United Kingdom United States
Contacts
Name:     Head of Clinical Development
Address: 
Telephone: +46 8 615 20 40
Email: trials@oncopeptides.se
Affiliation: 
Name:     Giovanni Palladini, MD
Address: 
Telephone:
Email:
Affiliation:  University Hospital San Matteo in Pavia
Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All
Health Condition(s) or Problem(s) studied
AL Amyloidosis
Intervention(s)
Drug: Dexamethasone
Drug: Melphalan-Flufenamide (Melflufen)
Primary Outcome(s)
The primary endpoint in Phase 2 is to evaluate the hematologic overall response rate (ORR) after 4 cycles at the RP2D determined in Phase 1 [Time Frame: During phase 2 after 4 cycles of treatment ( approx. 4 months)]
The primary objective in Phase 1 is to explore safety and tolerability of melflufen [Time Frame: During phase 1 for up to 8 cycles of treatment of 28 days each (approx. up to 8 months)]
The primary objective in Phase 1 is to identify recommended Phase 2 dose (RP2D) [Time Frame: During phase 1 for up to 8 cycles of 28 days each (approx. up to 8 months)]
Secondary Outcome(s)
To assess best hematologic response [Time Frame: Throughout the study treatment of up to 8 cycles of 28 days each (approx. 8 months) per patient]
To assess duration of organ system responses [Time Frame: Throughout the study treatment period of up to 8 cycles (approx 8 months) per patient]
To assess hematologic ORR (overall response rate) [Time Frame: During phase 1 for up to 8 cycles of treatment of 28 days each (approx. up to 8 months)]
To assess Overall Survival (OS) [Time Frame: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and up to 24 months of follow up]
To assess pharmacokinetic profile of melflufen in this patient population [Time Frame: At Cycle 1 Day 1 and Cycle 2 Day 1 at time points 5-10 minutes, 1-2 hours and 3-8 hours after end of infusion. Each cycle length is 28 days.]
To assess the duration of hematologic response [Time Frame: Throughout the study treatment period of up to 8 cycles of 28 days each (approx 8 months) per patient]
To assess the proportion of organ system responses [Time Frame: Throughout the study treatment period of up to 8 cycles of 28 days each (approx 8 months) per patient]
To assess time to next AL amyloidosis treatment [Time Frame: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and 24 months of follow up]
Secondary ID(s)
OP201
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
PRA Health Sciences
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
Disclaimer: Trials posted on this search portal are not endorsed by WHO, but are provided as a service to our users. In no event shall the World Health Organization be liable for any damages arising from the use of the information linked to in this section. None of the information obtained through use of the search portal should in any way be used in clinical care without consulting a physician or licensed health professional. WHO is not responsible for the accuracy, completeness and/or use made of the content displayed for any trial record.
Copyright - World Health Organization - Version 3.6 - Version history