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

NCT04649060 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: OP-1082019-002161-36
• Study Type: interventional
• Target: 54
• Locations: 11 countries
• Sites: 26

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Overall Response Rate (ORR)

  From the date of randomization until the end of study (approximately 12 months).

• Duration of Response (DOR)

  From the date of randomization until the end of study (approximately 12 months).

• Best Response

  From the date of randomization until the end of study (approximately 12 months).

• Clinical Benefit Rate (CBR)

  From the date of randomization until the end of study (approximately 12 months).

• Duration of Clinical Benefit (DOCB)

  From the date of randomization until the end of study (approximately 12 months).

Study Arms (2)

Arm A (melflufen+dexamethasone+daratumumab)

EXPERIMENTAL

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

Drug: Melflufen; Drug: Dexamethasone; Drug: Daratumumab

Arm B (daratumumab)

ACTIVE COMPARATOR

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

Drug: Daratumumab

Interventions

Melflufen DRUG

Powder for solution for i.v. infusion

Also known as: Melphalan Flufenamide, Pepaxto, Pepaxti

Arm A (melflufen+dexamethasone+daratumumab)

Dexamethasone DRUG

Oral tablets

Also known as: Dex

Arm A (melflufen+dexamethasone+daratumumab)

Daratumumab DRUG

Solution for s.c. injection

Also known as: Darzalex FASPRO

Arm A (melflufen+dexamethasone+daratumumab); Arm B (daratumumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oncopeptides AB: lead

Study Sites (26)

University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic

Plovdiv, Bulgaria

Location

Specialized Hospital for Active Treatment of Hematological Diseases, Clinical Hematology Clinic

Sofia, Bulgaria

Location

University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology

Brno, 62500, Czechia

Location

University Hospital Hradec Kralove, 4th Internal Clinic of Hematology

Kralovice, Czechia

Location

University Hospital Ostrava, Clinic of Hematooncology

Ostrava-Poruba, Czechia

Location

General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology

Prague, Czechia

Location

JSC K. Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, Georgia

Location

Malkhaz Katsiashvili Multiprofile EMC LTD

Tbilisi, Georgia

Location

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

Siegen, Germany

Location

Alexandra General Hospital, Therapeutic Clinic

Athens, Greece

Location

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

Athens, Greece

Location

Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center

Oslo, Norway

Location

Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases

Chorzów, Poland

Location

University Clinical Center, Teaching Department of Hematology and Transplantology

Gdansk, Poland

Location

Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department

Krakow, Poland

Location

Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz

Lodz, Poland

Location

St. John of Dukla Oncology Center of Lublin Region, Department of Hematology and Bone Marrow Transplantation

Lublin, Poland

Location

Leningrad Regional Clinical Hospital

Saint Petersburg, Russia

Location

V.D. Seredavin Samara Regional Clinical Hospital

Samara, Russia

Location

Clinical Center of Serbia

Belgrade, Serbia

Location

Hospital Clinic of Barcelona, Department of Hematology

Barcelona, Spain

Location

Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center

Cherkasy, Ukraine

Location

Chernihiv Medical Center of Modern Oncology, Hematology Department

Chernihiv, Ukraine

Location

City Clinical Hospital No. 4 City Hematology Center

Dnipro, Ukraine

Location

Kyiv City Clinical Hospital No. 9, Hematology Department No. 1

Kyiv, Ukraine

Location

National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group

Kyiv, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 37646660 DERIVED

• 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.

  PMID: 37646657 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

melflufen; L-melphalanyl-p-L-fluorophenylalanine ethyl ester; Dexamethasone; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

This study was put on clinical hold and later discontinued prematurely. Due to this, there is limited data available, and data cleaning was not done according to the original plan. Due to the early termination, the response assessments were done by investigators, not by an independent review committee.

Results Point of Contact

• Title: VP Chief Operating Officer
• Organization: Oncopeptides AB

trials@oncopeptides.com

+46 8 615 20 40

Study Officials

• Maria-Victorìa Mateos, MD, PhD

  Complejo Hospitalario de Salamanca

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 2, 2020
• Study Start: December 21, 2020
• Primary Completion: February 7, 2022
• Study Completion: February 7, 2022
• Last Updated: June 8, 2023
• Results First Posted: June 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); GE (2); PL (5); GR (2); UA (5); DE (1); BU (2); ES (1); CZ (4); RU (2); NO (1)