Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma

Relapsed Multiple Myeloma Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04649060
• Other study ID #: OP-108
• Secondary ID: 2019-002161-36
• Status: Terminated
• Phase: Phase 3
• Start date: December 21, 2020
• Est. completion date: February 7, 2022

Study information

• Verified date: February 2023
• Source: Oncopeptides AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. completion date: February 7, 2022
• Est. primary completion date: February 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed Multiple Myeloma

Intervention

Drug:
• Melflufen
Powder for solution for i.v. infusion
• Dexamethasone
Oral tablets
• Daratumumab
Solution for s.c. injection

Locations

Country	Name	City	State
Bulgaria	University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic	Plovdiv
Bulgaria	Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic	Sofia
Czechia	University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology	Brno
Czechia	University Hospital Hradec Kralove, 4th Internal Clinic of Hematology	Kralovice
Czechia	University Hospital Ostrava, Clinic of Hematooncology	Ostrava-Poruba
Czechia	General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology	Prague
Georgia	JSC K. Eristavi National Center of Experimental and Clinical Surgery	Tbilisi
Georgia	Malkhaz Katsiashvili Multiprofile EMC LTD	Tbilisi
Germany	St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine	Siegen
Greece	Alexandra General Hospital, Therapeutic Clinic	Athens
Greece	General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma	Athens
Norway	Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center	Oslo
Poland	Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases	Chorzów
Poland	University Clinical Center, Teaching Department of Hematology and Transplantology	Gdansk
Poland	Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department	Kraków
Poland	Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz	Lodz
Poland	St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation	Lublin
Russian Federation	Leningrad Regional Clinical Hospital	Saint Petersburg
Russian Federation	V.D. Seredavin Samara Regional Clinical Hospital	Samara
Serbia	Clinical Center of Serbia	Belgrade
Spain	Hospital Clinic of Barcelona, Department of Hematology	Barcelona
Ukraine	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	National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group	Kyiv

Sponsors (1)

Lead Sponsor	Collaborator
Oncopeptides AB

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Georgia,  Germany,  Greece,  Norway,  Poland,  Russian Federation,  Serbia,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the date of randomization until the end of study (approximately 12 months).
Secondary	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).	From the date of randomization until the end of study (approximately 12 months).
Secondary	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.	From the date of randomization until the end of study (approximately 12 months).
Secondary	Best Response	Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).	From the date of randomization until the end of study (approximately 12 months).
Secondary	Clinical Benefit Rate (CBR)	The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.	From the date of randomization until the end of study (approximately 12 months).
Secondary	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.	From the date of randomization until the end of study (approximately 12 months).
Secondary	Time to Response (TTR)	Time from randomization to the date of the first documented confirmed response in a patient who has responded with =PR.	From the date of randomization until the end of study (approximately 12 months).
Secondary	Time to Progression (TTP)	Time from randomization to the date of the first documented confirmed PD	From the date of randomization until the end of study (approximately 12 months).
Secondary	Time to Next Treatment (TTNT)	Time from randomization to the date of next anti-myeloma treatment or until death.	From the date of randomization until the end of study (approximately 12 months).
Secondary	Overall Survival (OS)	Time from randomization to death due to any cause.	From the date of randomization until the end of study (approximately 12 months).