Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma
- Conditions
- Relapsed Multiple MyelomaRelapsed-Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT04649060
- Lead Sponsor
- Oncopeptides AB
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 54
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (melflufen+dexamethasone+daratumumab) Dexamethasone 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 A (melflufen+dexamethasone+daratumumab) Daratumumab 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 B (daratumumab) Daratumumab 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 Arm A (melflufen+dexamethasone+daratumumab) Melflufen 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
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) 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.
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) From the date of randomization until the end of study (approximately 12 months). 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) From the date of randomization until the end of study (approximately 12 months). 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.
Overall Survival (OS) From the date of randomization until the end of study (approximately 12 months). Time from randomization to death due to any cause.
Time to Response (TTR) From the date of randomization until the end of study (approximately 12 months). Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.
Best Response From the date of randomization until the end of study (approximately 12 months). Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).
Clinical Benefit Rate (CBR) From the date of randomization until the end of study (approximately 12 months). The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.
Duration of Clinical Benefit (DOCB) From the date of randomization until the end of study (approximately 12 months). 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 Progression (TTP) From the date of randomization until the end of study (approximately 12 months). Time from randomization to the date of the first documented confirmed PD
Time to Next Treatment (TTNT) From the date of randomization until the end of study (approximately 12 months). Time from randomization to the date of next anti-myeloma treatment or until death.
Trial Locations
- Locations (26)
Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department
🇵🇱Kraków, Poland
Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic
🇧🇬Sofia, Bulgaria
University Hospital Hradec Kralove, 4th Internal Clinic of Hematology
🇨🇿Kralovice, Czechia
University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic
🇧🇬Plovdiv, Bulgaria
St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation
🇵🇱Lublin, Poland
Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
🇵🇱Lodz, Poland
General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma
🇬🇷Athens, Greece
National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group
🇺🇦Kyiv, Ukraine
Malkhaz Katsiashvili Multiprofile EMC LTD
🇬🇪Tbilisi, Georgia
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
🇨🇿Brno, Czechia
General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology
🇨🇿Prague, Czechia
University Hospital Ostrava, Clinic of Hematooncology
🇨🇿Ostrava-Poruba, Czechia
Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases
🇵🇱Chorzów, Poland
Alexandra General Hospital, Therapeutic Clinic
🇬🇷Athens, Greece
St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine
🇩🇪Siegen, Germany
University Clinical Center, Teaching Department of Hematology and Transplantology
🇵🇱Gdańsk, Poland
Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center
🇳🇴Oslo, Norway
V.D. Seredavin Samara Regional Clinical Hospital
🇷🇺Samara, Russian Federation
Leningrad Regional Clinical Hospital
🇷🇺Saint Petersburg, Russian Federation
Hospital Clinic of Barcelona, Department of Hematology
🇪🇸Barcelona, Spain
JSC K. Eristavi National Center of Experimental and Clinical Surgery
🇬🇪Tbilisi, Georgia
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center
🇺🇦Cherkasy, Ukraine
Chernihiv Medical Center of Modern Oncology, Hematology Department
🇺🇦Chernihiv, Ukraine
City Clinical Hospital No. 4 City Hematology Center
🇺🇦Dnipro, Ukraine
Kyiv City Clinical Hospital No. 9, Hematology Department No. 1
🇺🇦Kyiv, Ukraine