Relapsed Multiple MyelomaPhase 3LIGHTHOUSENCT04649060
Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma
A Phase 3 study testing Melflufen, Dexamethasone and Daratumumab in people with Relapsed Multiple Myeloma and Relapsed-Refractory Multiple Myeloma, run by Oncopeptides AB at 26 sites in 11 countries.
Trial summary
This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with Relapsed-Refractory Multiple Myeloma (RRMM) who were either double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or had received at… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Multiple Myeloma, Relapsed-Refractory Multiple Myeloma
- What is being tested?
- Melflufen, Dexamethasone and Daratumumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 26 sitesin 11 countries
- Study dates
- 21 Dec 2020to 7 Feb 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- A prior diagnosis of multiple myeloma with documented disease progression after the last line of therapy
- Double refractory to an IMiD and a PI (regardless of the number of prior lines of therapy) or have received at least 3 prior lines of therapy including an IMiD and a PI
- Prior treatment with daratumumab or another anti-CD38 antibody may be allowed under certain circumstances:
- Achieved at least partial response (PR) and not refractory to an anti-CD38 antibody
- At least 6 months since the last dose of anti-CD38 antibody
- Not discontinued anti-CD38 antibody treatment due to related Grade ≥ 3 toxicity
- Male and female of childbearing potential agree to use contraception during the treatment period and at least 3 months after the last dose
Who cannot join
- Primary refractory disease (i.e., never responded with at least Minimal Response to any prior therapy for multiple myeloma)
- Prior treatment with CD38 CAR-T cell therapy or CD38/CD3 bispecific antibodies
- Any medical condition that may interfere with safety or participation in this study
- Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast, or very low and low-risk prostate cancer in active surveillance
- Known or suspected amyloidosis, plasma cell leukemia, or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Known central nervous system (CNS) or meningeal involvement of myeloma
- Prior stem cell transplant (autologous and/or allogenic) within 6 months of initiation of therapy or prior allogeneic stem cell transplantation with active graft-versus-host-disease
- Prior treatment with melflufen
Trial locations and contacts
26 sites in 11 countries.
26 sites in 11 countries
Poland5 sites
Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases
Chorzów
University Clinical Center, Teaching Department of Hematology and Transplantology
Gdansk
Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department
Krakow
Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
Lodz
St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation
Lublin
Ukraine5 sites
Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center
Cherkasy
Chernihiv Medical Center of Modern Oncology, Hematology Department
Chernihiv
City Clinical Hospital No. 4 City Hematology Center
Dnipro
Kyiv City Clinical Hospital No. 9, Hematology Department No. 1
Kyiv
National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group
Kyiv
Czechia4 sites
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
Brno, 62500
University Hospital Hradec Kralove, 4th Internal Clinic of Hematology
Kralovice
University Hospital Ostrava, Clinic of Hematooncology
Ostrava-Poruba
General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology
Prague
Bulgaria2 sites
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic
Plovdiv
Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic
Sofia
Georgia2 sites
JSC K. Eristavi National Center of Experimental and Clinical Surgery
Tbilisi
Malkhaz Katsiashvili Multiprofile EMC LTD
Tbilisi
Greece2 sites
Alexandra General Hospital, Therapeutic Clinic
Athens
General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma
Athens
Russia2 sites
Leningrad Regional Clinical Hospital
Saint Petersburg
V.D. Seredavin Samara Regional Clinical Hospital
Samara
Germany1 site
St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine
Siegen
Norway1 site
Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center
Oslo
About this study
Official title: A Randomized, Controlled, Open-Label Phase 3 Study of Melflufen in Combination With Daratumumab Compared With Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma
This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with Relapsed-Refractory Multiple Myeloma (RRMM) who were either double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or had received at least 3 prior lines of therapy including an IMiD and a PI.
Patients received treatment with melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity, or patient/treating physician decision. Patients in the daratumumab treatment arm had the option to receive treatment with melflufen+dexamethasone+daratumumab after confirmed progressive disease.
- Being tested
- Melflufen, Dexamethasone, Daratumumab
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelflufenDrug
Also called Melphalan Flufenamide, Pepaxto, Pepaxti
Powder for solution for i.v. infusion
DexamethasoneDrug
Also called Dex
Oral tablets
DaratumumabDrug
Also called Darzalex FASPRO
Solution for s.c. injection
| Study group | Role | What they receive |
|---|---|---|
| Arm A (melflufen+dexamethasone+daratumumab) | Experimental | Treatment was given in 28-day cycles in an outpatient treatment setting.
* Melflufen 30 mg intravenous (i.v.) infusion on Day 1 of each cycle
* Dexamethasone 40 mg per oral (p.o.) weekly (20 mg p.o. weekly if ≥75 years)
* Daratumumab 1800 mg subcutaneously (s.c.) on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7 Receives: Drug: Melflufen; Drug: Dexamethasone; Drug: Daratumumab |
| Arm B (daratumumab) | Active comparator | Treatment was given in 28-day cycles in an outpatient treatment setting.
• Daratumumab 1800 mg s.c. on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7 Receives: Drug: Daratumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Time from the date of randomization to the date of first documentation of confirmed progressive disease (PD) or death due to any cause, whichever occurred first.
Measured: From the date of randomization until the end of study (approximately 12 months).
Secondary outcomes (9)
Overall Response Rate (ORR)
Proportion of patients who achieve a best-confirmed response of stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR).
Measured: From the date of randomization until the end of study (approximately 12 months).
Duration of Response (DOR)
Time from the first evidence of confirmed assessment of sCR, CR, VGPR or PR to first confirmed disease progression, or death due to any cause. DOR is defined only for patients with a confirmed PR or better.
Measured: From the date of randomization until the end of study (approximately 12 months).
Best Response
Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).
Measured: From the date of randomization until the end of study (approximately 12 months).
Clinical Benefit Rate (CBR)
The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.
Measured: From the date of randomization until the end of study (approximately 12 months).
Duration of Clinical Benefit (DOCB)
Time from first evidence of confirmed assessment of sCR, CR, VGPR, PR, or MR to first confirmed disease progression, or to death due to any cause. DOCB is defined only for patients with a confirmed MR or better.
Measured: From the date of randomization until the end of study (approximately 12 months).
Time to Response (TTR)
Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.
Measured: From the date of randomization until the end of study (approximately 12 months).
Time to Progression (TTP)
Time from randomization to the date of the first documented confirmed PD
Measured: From the date of randomization until the end of study (approximately 12 months).
Time to Next Treatment (TTNT)
Time from randomization to the date of next anti-myeloma treatment or until death.
Measured: From the date of randomization until the end of study (approximately 12 months).
Overall Survival (OS)
Time from randomization to death due to any cause.
Measured: From the date of randomization until the end of study (approximately 12 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2020
- Study start21 Dec 2020
- Primary completion7 Feb 2022
- Study completion7 Feb 2022
Why it stopped: The sponsor decided to terminate the study due to financial issues following an FDA request for a partial clinical hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Relapsed Multiple MyelomaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncopeptides AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Maria-Victorìa Mateos, MD, PhD, Principal investigator, Complejo Hospitalario de Salamanca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04649060
- Sponsor's protocol ID
- OP-108
- Other IDs
- 2019-002161-36, 2019
- Acronym
- LIGHTHOUSE
- Status last verified
- Feb 2023
- First submitted
- 24 Nov 2020
- Last updated
- 8 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pour L, Szarejko M, Bila J, Schjesvold FH, Spicka I, Maisnar V, Jurczyszyn A, Grudeva-Popova Z, Hajek R, Usenko G, Thuresson M, Norin S, Jarefors S, Bakker NA, Richardson PG, Mateos MV. Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study. Haematologica. 2024 Mar 1;109(3):895-905. doi: 10.3324/haematol.2023.283509.
PubMed 37646660Ocio EM, Efebera YA, Hajek R, Straub J, Maisnar V, Eveillard JR, Karlin L, Mateos MV, Oriol A, Ribrag V, Richardson PG, Norin S, Obermuller J, Bakker NA, Pour L. ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study. Haematologica. 2024 Mar 1;109(3):867-876. doi: 10.3324/haematol.2023.283490.
PubMed 37646657
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled, Open-Label Phase 3 Study of Melflufen in Combination With Daratumumab Compared With Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04649060
- Acronym / sponsor ID
- LIGHTHOUSE / OP-108
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to terminate the study due to financial issues following an FDA request for a partial clinical hold.
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Oncopeptides ABIndustry (pharma, biotech, devices)
- Study start
- 21 Dec 2020 (actual)
- Primary completion
- 7 Feb 2022 (actual)
- Study completion
- 7 Feb 2022 (actual)
- First posted
- 2 Dec 2020 (actual)
- Results
- Posted 8 Jun 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with Relapsed-Refractory Multiple Myeloma (RRMM) who were either double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or had received at least 3 prior lines of therapy including an IMiD and a PI.
Patients received treatment with melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity, or patient/treating physician decision. Patients in the daratumumab treatment arm had the option to receive treatment with melflufen+dexamethasone+daratumumab after confirmed progressive disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (melflufen+dexamethasone+daratumumab) | Experimental | Drug: Melflufen, Drug: Dexamethasone, Drug: DaratumumabTreatment was given in 28-day cycles in an outpatient treatment setting. * Melflufen 30 mg intravenous (i.v.) infusion on Day 1 of each cycle * Dexamethasone 40 mg per oral (p.o.) weekly (20 mg p.o. weekly if ≥75 years) * Daratumumab 1800 mg subcutaneously (s.c.) on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7 |
| Arm B (daratumumab) | Active comparator | Drug: DaratumumabTreatment was given in 28-day cycles in an outpatient treatment setting. • Daratumumab 1800 mg s.c. on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- A prior diagnosis of multiple myeloma with documented disease progression after the last line of therapy
- Double refractory to an IMiD and a PI (regardless of the number of prior lines of therapy) or have received at least 3 prior lines of therapy including an IMiD and a PI
- Prior treatment with daratumumab or another anti-CD38 antibody may be allowed under certain circumstances:
- Male and female of childbearing potential agree to use contraception during the treatment period and at least 3 months after the last dose
Key exclusion criteria (8 listed)
- Primary refractory disease (i.e., never responded with at least Minimal Response to any prior therapy for multiple myeloma)
- Prior treatment with CD38 CAR-T cell therapy or CD38/CD3 bispecific antibodies
- Any medical condition that may interfere with safety or participation in this study
- Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast, or very low and low-risk prostate cancer in active surveillance
- Known or suspected amyloidosis, plasma cell leukemia, or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
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 |
|---|---|---|
| MelflufenAlso: Melphalan Flufenamide, Pepaxto, PepaxtiPowder for solution for i.v. infusion | Drug | Arm A (melflufen+dexamethasone+daratumumab) |
| DexamethasoneAlso: DexOral tablets | Drug | Arm A (melflufen+dexamethasone+daratumumab) |
| DaratumumabAlso: Darzalex FASPROSolution for s.c. injection | Drug | Arm A (melflufen+dexamethasone+daratumumab), Arm B (daratumumab) |
Primary outcome
Progression Free Survival (PFS)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Time from the date of randomization to the date of first documentation of confirmed progressive disease (PD) or death due to any cause, whichever occurred first.
9 secondary outcomes
Overall Response Rate (ORR)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Duration of Response (DOR)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Best Response
Time frame: From the date of randomization until the end of study (approximately 12 months).
Clinical Benefit Rate (CBR)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Duration of Clinical Benefit (DOCB)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Time to Response (TTR)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Time to Progression (TTP)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Time to Next Treatment (TTNT)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Overall Survival (OS)
Time frame: From the date of randomization until the end of study (approximately 12 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37646660Pour L, Szarejko M, Bila J, Schjesvold FH, Spicka I, Maisnar V, Jurczyszyn A, Grudeva-Popova Z, Hajek R, Usenko G, Thuresson M, Norin S, Jarefors S, Bakker NA, Richardson PG, Mateos MV. Efficacy and safety of melflufen plus daratumumab and dexamethasone in relapsed/refractory multiple myeloma: results from the randomized, open-label, phase III LIGHTHOUSE study. Haematologica. 2024 Mar 1;109(3):895-905. doi: 10.3324/haematol.2023.283509.
- Derived from this study: PubMed 37646657Ocio EM, Efebera YA, Hajek R, Straub J, Maisnar V, Eveillard JR, Karlin L, Mateos MV, Oriol A, Ribrag V, Richardson PG, Norin S, Obermuller J, Bakker NA, Pour L. ANCHOR: melflufen plus dexamethasone and daratumumab or bortezomib in relapsed/refractory multiple myeloma: final results of a phase I/IIa study. Haematologica. 2024 Mar 1;109(3):867-876. doi: 10.3324/haematol.2023.283490.
- Individual participant dataSharing planned: No
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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.
Maria-Victorìa Mateos, MD, PhD principal investigator
Complejo Hospitalario de Salamanca
26 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Melflufen, Dexamethasone and Daratumumab in people with Relapsed Multiple Myeloma and Relapsed-Refractory Multiple Myeloma, run by Oncopeptides AB at 26 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. 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 8 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Poland, Ukraine, Czechia, Bulgaria, Georgia and 6 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression Free Survival (PFS) (time frame: From the date of randomization until the end of study (approximately 12 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04649060, which also lists 2 linked publications.
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 8 Jun 2023.