Back to resultsStudy of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma (LIGHTHOUSE)
Primary Purpose
Relapsed Multiple Myeloma, Relapsed-Refractory Multiple Myeloma
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Melflufen
Dexamethasone
Daratumumab
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- A prior diagnosis of multiple myeloma with documented disease progression after last line of therapy
- Double refractory to an immunomodulatory drug (IMiD) and a Proteasome Inhibitor (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 women of childbearing potential agrees to use contraception during the treatment period and during a specified time period after the last dose
Exclusion criteria:
- 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
Sites / Locations
- University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic
- Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic
- University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
- University Hospital Hradec Kralove, 4th Internal Clinic of Hematology
- University Hospital Ostrava, Clinic of Hematooncology
- General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology
- JSC K. Eristavi National Center of Experimental and Clinical Surgery
- Malkhaz Katsiashvili Multiprofile EMC LTD
- St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine
- Alexandra General Hospital, Therapeutic Clinic
- General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma
- Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center
- Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases
- University Clinical Center, Teaching Department of Hematology and Transplantology
- Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department
- Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
- St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation
- Leningrad Regional Clinical Hospital
- V.D. Seredavin Samara Regional Clinical Hospital
- Clinical Center of Serbia
- Hospital Clinic of Barcelona, Department of Hematology
- Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center
- Chernihiv Medical Center of Modern Oncology, Hematology Department
- City Clinical Hospital No. 4 City Hematology Center
- Kyiv City Clinical Hospital No. 9, Hematology Department No. 1
- National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A (melflufen+dexamethasone+daratumumab)
Arm B (daratumumab)
Arm Description
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
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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
Best Response
Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).
Clinical Benefit Rate (CBR)
The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.
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.
Time to Response (TTR)
Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.
Time to Progression (TTP)
Time from randomization to the date of the first documented confirmed PD
Time to Next Treatment (TTNT)
Time from randomization to the date of next anti-myeloma treatment or until death.
Overall Survival (OS)
Time from randomization to death due to any cause.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04649060
Brief Title
Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma
Acronym
LIGHTHOUSE
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
The sponsor decided to terminate the study due to financial issues following an FDA request for a partial clinical hold.
Study Start Date
December 21, 2020 (Actual)
Primary Completion Date
February 7, 2022 (Actual)
Study Completion Date
February 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oncopeptides AB
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Multiple Myeloma, Relapsed-Refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Independent Review Committee was planned to be blinded to treatment assignment. Due to the early termination, the response assessments were only done by investigators, not by an independent review committee.
Allocation
Randomized
Enrollment
54 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (melflufen+dexamethasone+daratumumab)
Arm Type
Experimental
Arm Description
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
Arm Title
Arm B (daratumumab)
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Melflufen
Other Intervention Name(s)
Melphalan Flufenamide, Pepaxto, Pepaxti
Intervention Description
Powder for solution for i.v. infusion
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Dex
Intervention Description
Oral tablets
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Darzalex FASPRO
Intervention Description
Solution for s.c. injection
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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).
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Duration of Response (DOR)
Description
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.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Best Response
Description
Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Clinical Benefit Rate (CBR)
Description
The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Duration of Clinical Benefit (DOCB)
Description
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.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Time to Response (TTR)
Description
Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Time to Progression (TTP)
Description
Time from randomization to the date of the first documented confirmed PD
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Time to Next Treatment (TTNT)
Description
Time from randomization to the date of next anti-myeloma treatment or until death.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
Title
Overall Survival (OS)
Description
Time from randomization to death due to any cause.
Time Frame
From the date of randomization until the end of study (approximately 12 months).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria-Victorìa Mateos, MD, PhD
Organizational Affiliation
Complejo Hospitalario de Salamanca
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic
City
Plovdiv
Country
Bulgaria
Facility Name
Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic
City
Sofia
Country
Bulgaria
Facility Name
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
City
Brno
ZIP/Postal Code
62500
Country
Czechia
Facility Name
University Hospital Hradec Kralove, 4th Internal Clinic of Hematology
City
Kralovice
Country
Czechia
Facility Name
University Hospital Ostrava, Clinic of Hematooncology
City
Ostrava-Poruba
Country
Czechia
Facility Name
General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology
City
Prague
Country
Czechia
Facility Name
JSC K. Eristavi National Center of Experimental and Clinical Surgery
City
Tbilisi
Country
Georgia
Facility Name
Malkhaz Katsiashvili Multiprofile EMC LTD
City
Tbilisi
Country
Georgia
Facility Name
St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine
City
Siegen
Country
Germany
Facility Name
Alexandra General Hospital, Therapeutic Clinic
City
Athens
Country
Greece
Facility Name
General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma
City
Athens
Country
Greece
Facility Name
Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center
City
Oslo
Country
Norway
Facility Name
Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases
City
Chorzów
Country
Poland
Facility Name
University Clinical Center, Teaching Department of Hematology and Transplantology
City
Gdańsk
Country
Poland
Facility Name
Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department
City
Kraków
Country
Poland
Facility Name
Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
City
Lodz
Country
Poland
Facility Name
St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation
City
Lublin
Country
Poland
Facility Name
Leningrad Regional Clinical Hospital
City
Saint Petersburg
Country
Russian Federation
Facility Name
V.D. Seredavin Samara Regional Clinical Hospital
City
Samara
Country
Russian Federation
Facility Name
Clinical Center of Serbia
City
Belgrade
Country
Serbia
Facility Name
Hospital Clinic of Barcelona, Department of Hematology
City
Barcelona
Country
Spain
Facility Name
Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center
City
Cherkasy
Country
Ukraine
Facility Name
Chernihiv Medical Center of Modern Oncology, Hematology Department
City
Chernihiv
Country
Ukraine
Facility Name
City Clinical Hospital No. 4 City Hematology Center
City
Dnipro
Country
Ukraine
Facility Name
Kyiv City Clinical Hospital No. 9, Hematology Department No. 1
City
Kyiv
Country
Ukraine
Facility Name
National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group
City
Kyiv
Country
Ukraine
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma
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