Clinical trial NCT04649060: Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma
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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsed Multiple Myeloma
Relapsed-Refractory Multiple Myeloma
Lead sponsor: Oncopeptides AB
Sponsor class: INDUSTRY
First posted: 2020-12-02
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Duration of Response (DOR)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Best Response
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Clinical Benefit Rate (CBR)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Duration of Clinical Benefit (DOCB)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Time to Response (TTR)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Time to Progression (TTP)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Time to Next Treatment (TTNT)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
measure: Overall Survival (OS)
timeFrame: From the date of randomization until the end of study (approximately 12 months).
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic
city: Brno
country: Czechia
facility: University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
city: Kralovice
country: Czechia
facility: University Hospital Hradec Kralove, 4th Internal Clinic of Hematology
city: Ostrava-Poruba
country: Czechia
facility: University Hospital Ostrava, Clinic of Hematooncology
city: Prague
country: Czechia
facility: General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology
city: Tbilisi
country: Georgia
facility: JSC K. Eristavi National Center of Experimental and Clinical Surgery
city: Tbilisi
country: Georgia
facility: Malkhaz Katsiashvili Multiprofile EMC LTD
city: Siegen
country: Germany
facility: St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine
city: Athens
country: Greece
facility: Alexandra General Hospital, Therapeutic Clinic
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma
city: Oslo
country: Norway
facility: Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center
city: Chorzów
country: Poland
facility: Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases
city: Gdańsk
country: Poland
facility: University Clinical Center, Teaching Department of Hematology and Transplantology
city: Kraków
country: Poland
facility: Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department
city: Lodz
country: Poland
facility: Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz
city: Lublin
country: Poland
facility: St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
city: Samara
country: Russian Federation
facility: V.D. Seredavin Samara Regional Clinical Hospital
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona, Department of Hematology
city: Cherkasy
country: Ukraine
facility: Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center
city: Chernihiv
country: Ukraine
facility: Chernihiv Medical Center of Modern Oncology, Hematology Department
city: Dnipro
country: Ukraine
facility: City Clinical Hospital No. 4 City Hematology Center
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital No. 9, Hematology Department No. 1
city: Kyiv
country: Ukraine
facility: National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group
Study officials:
affiliation: Complejo Hospitalario de Salamanca
name: Maria-Victorìa Mateos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: