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

NCT ID: NCT04649060

Last Updated: 2023-06-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-21
• Study Completion Date: 2022-02-07

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.

Conditions

Relapsed Multiple Myeloma; Relapsed-Refractory Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Arm A (melflufen+dexamethasone+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

Group Type: EXPERIMENTAL

Melflufen

Intervention Type: DRUG

Powder for solution for i.v. infusion

Dexamethasone

Intervention Type: DRUG

Oral tablets

Daratumumab

Intervention Type: DRUG

Solution for s.c. injection

Arm B (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

Group Type: ACTIVE_COMPARATOR

Daratumumab

Intervention Type: DRUG

Solution for s.c. injection

Interventions

Melflufen

Powder for solution for i.v. infusion

Intervention Type: DRUG

Dexamethasone

Oral tablets

Intervention Type: DRUG

Daratumumab

Solution for s.c. injection

Intervention Type: DRUG

Other Intervention Names

Melphalan Flufenamide; Pepaxto; Pepaxti; Dex; Darzalex FASPRO

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oncopeptides AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria-Victorìa Mateos, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Complejo Hospitalario de Salamanca

Locations

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, , Bulgaria

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, , Czechia

JSC K. Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, , Georgia

Malkhaz Katsiashvili Multiprofile EMC LTD

Tbilisi, , Georgia

St. Marien-Hospital Siegen gem. GmbH, Clinic for Hematology, Medical Oncology and Palliative Medicine

Siegen, , Germany

Alexandra General Hospital, Therapeutic Clinic

Athens, , Greece

General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma

Athens, , Greece

Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center

Oslo, , Norway

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

Krakow, , 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, , Poland

Leningrad Regional Clinical Hospital

Saint Petersburg, , Russia

V.D. Seredavin Samara Regional Clinical Hospital

Samara, , Russia

Clinical Center of Serbia

Belgrade, , Serbia

Hospital Clinic of Barcelona, Department of Hematology

Barcelona, , Spain

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, , Ukraine

Countries

Bulgaria; Czechia; Georgia; Germany; Greece; Norway; Poland; Russia; Serbia; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 37646660 (View on PubMed)

Ocio 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.

Reference Type: DERIVED

PMID: 37646657 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002161-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OP-108

Identifier Type: -

Identifier Source: org_study_id