A Phase 1 interventional study of Melphalan-Flufenamide (Melflufen) and Dexamethasone in AL Amyloidosis, sponsored by Oncopeptides AB. Terminated at 9 sites in 9 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-03-28.
Sponsored by Oncopeptides AB · Phase 1, Interventional, and Treatment
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.
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.
167 studies on the registry are indexed under Immunoglobulin Light-chain Amyloidosis; 57 are open to participants now.
This study's enrollment of 6 is below the median of 37 across 120 interventional studies indexed under Immunoglobulin Light-chain Amyloidosis.
Browse Immunoglobulin Light-chain Amyloidosis studies →Oncopeptides AB is the lead sponsor of 10 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 5 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria: (For full list of inclusion criteria, see study protocol)
Exclusion Criteria: (For full list of exclusion criteria, see study protocol)
Intravenous infusion of melflufen Day 1 of 28 day cycles, in combination of dexamethasone on Days 1 and 2 of each 28-day cycle.
Drug: Melphalan-Flufenamide (Melflufen) · Drug: Dexamethasone
Treatment consist of i.v. melflufen on Day 1 of each 28-day cycle.
Dexamethasone 40 mg (20 mg at investigator's discretion) administered on Days 1 and 2 of each 28-day cycle.
Also known as: Dexamethason JENAPHARM
The primary objective in Phase 1 is to explore safety and tolerability of melflufen
Endpoints: * Frequency and grade of Adverse Events. The maximum grade for each type of AE will be recorded for each participant and frequency tables will be presented and reviewed to determine patterns * Laboratory values (laboratory abnormalities) for hematology, coagulation, blood chemistry, urinalysis
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)
Endpoint: Dose-Limiting Toxicity (DLT) during Cycle 1 up to maximum dose of melflufen of 40 mg. A DLT event is defined as thrombocytopenia, neutropenia, non-hematologic toxicity and/or inability to receive Cycle 2 Day 1 dose within 14 days from planned Cycle 2 Day 2 due to continued melflufen-related toxicity from Cycle 1.
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
The proportion of participants who achieve a hematologic Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
Time frame: During phase 2 after 4 cycles of treatment ( approx. 4 months)
To assess pharmacokinetic profile of melflufen in this patient population
Melphalan plasma concentration post melflufen administration at 3 time points
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 best hematologic response
Proportion of patients with each outcome (Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) or Progressive Disease (PD))
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
Median time (Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) or Progressive Disease (PD))
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
Proportion of participants with kidney, cardiac or liver response, respectively
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
Duration of organ responses separately for each organ
Time frame: Throughout the study treatment period of up to 8 cycles (approx 8 months) per patient
To assess hematologic ORR (overall response rate)
Proportion of participants who achieve a hematologic CR, VGPR or PR
Time frame: During phase 1 for up to 8 cycles of treatment of 28 days each (approx. up to 8 months)
To assess time to next AL amyloidosis treatment
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 Overall Survival (OS)
Overall survival
Time frame: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and up to 24 months of follow up
This study is terminated, as verified in Feb 2022. You cannot join it, but the record below documents what was studied.
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