AL AmyloidosisPhase 1NCT04115956
A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis
A Phase 1 study testing Melphalan-Flufenamide (Melflufen) and Dexamethasone in people with AL Amyloidosis, run by Oncopeptides AB at 9 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- Melphalan-Flufenamide (Melflufen) and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 9 sitesin 9 countries
- Study dates
- 6 Aug 2020to 5 Jan 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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 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: (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
Trial locations and contacts
9 sites in 9 countries.
9 sites in 9 countries
United States1 site
Boston University Medical Center
Boston, Massachusetts, 02111
United Kingdom1 site
University College London Hospitals NHS Foundation Trust
London, NW1 2BU
About this study
Official 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
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.
Read the 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
- Being tested
- Melphalan-Flufenamide (Melflufen), Dexamethasone
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Melphalan-Flufenamide (Melflufen)Drug
Treatment consist of i.v. melflufen on Day 1 of each 28-day cycle.
DexamethasoneDrug
Also called Dexamethason JENAPHARM
Dexamethasone 40 mg (20 mg at investigator's discretion) administered on Days 1 and 2 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Melflufen and dexamethasone in combination | Experimental | Intravenous infusion of melflufen Day 1 of 28 day cycles, in combination of dexamethasone on Days 1 and 2 of each 28-day cycle. Receives: Drug: Melphalan-Flufenamide (Melflufen); Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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)
Measured: During phase 2 after 4 cycles of treatment ( approx. 4 months)
Secondary outcomes (8)
To assess pharmacokinetic profile of melflufen in this patient population
Melphalan plasma concentration post melflufen administration at 3 time points
Measured: 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))
Measured: 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))
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and up to 24 months of follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2019
- Study start6 Aug 2020
- Primary completion5 Jan 2022
- Study completion5 Jan 2022
Why it stopped: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Melflufen + Dexamethasone
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncopeptides AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Giovanni Palladini, MD, Principal investigator, University Hospital San Matteo in Pavia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04115956
- Sponsor's protocol ID
- OP201
- Status last verified
- Feb 2022
- First submitted
- 29 Aug 2019
- Last updated
- 28 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04115956
- Acronym / sponsor ID
- OP201
- Conditions
- AL Amyloidosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Oncopeptides ABIndustry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 6 Aug 2020 (actual)
- Primary completion
- 5 Jan 2022 (actual)
- Study completion
- 5 Jan 2022 (actual)
- First posted
- 4 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Melflufen + Dexamethasone
| Arm | Type | Receives |
|---|---|---|
| Melflufen and dexamethasone in combination | Experimental | Drug: Melphalan-Flufenamide (Melflufen), Drug: DexamethasoneIntravenous infusion of melflufen Day 1 of 28 day cycles, in combination of dexamethasone on Days 1 and 2 of each 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Melphalan-Flufenamide (Melflufen)Treatment consist of i.v. melflufen on Day 1 of each 28-day cycle. | Drug | Melflufen and dexamethasone in combination |
| DexamethasoneAlso: Dexamethason JENAPHARMDexamethasone 40 mg (20 mg at investigator's discretion) administered on Days 1 and 2 of each 28-day cycle. | Drug | Melflufen and dexamethasone in combination |
Primary outcome
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)
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
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)
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.
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 proportion of participants who achieve a hematologic Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)
8 secondary outcomes
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 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 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 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)
Time frame: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and up to 24 months of follow up
Results and safety
The study was stopped early (reason given: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2022.
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Amyloidosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giovanni Palladini, MD principal investigator
University Hospital San Matteo in Pavia
9 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Melphalan-Flufenamide (Melflufen) and Dexamethasone in people with AL Amyloidosis, run by Oncopeptides AB at 9 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Czechia, France, Germany, Greece and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2022.