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

• Register: ClinicalTrials.gov
• Last refreshed on: 21 February 2022
• 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: 6
• Recruitment status: Terminated
• 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: Giovanni Palladini, MD
• 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 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)]

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)]

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 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 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 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]

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 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]

Secondary ID(s)

OP201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

PRA Health Sciences