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

Sponsor
Oncopeptides AB (Industry)
Overall Status
Terminated
CT.gov ID
NCT04649060
Collaborator
(none)
54
Enrollment
26
Locations
2
Arms
14
Actual Duration (Months)
2.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll patients that have Relapsed Refractory Multiple Myeloma and are double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (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.

Patients will receive treatment of melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity or patient/treating physician decision. Patients in the daratumumab treatment arm will after confirmed progressive disease have the option to receive treatment with melflufen+dexamethasone+daratumumab.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Masking Description:
Independent Review Committee will be blinded to treatment assignment
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 7, 2020
Actual Primary Completion Date :
Feb 7, 2022
Actual Study Completion Date :
Feb 7, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Study Treatment Arm A (melflufen+dexamethasone+daratumumab)

Treatment will be given in cycles and may be given in an outpatient treatment setting. Each cycle is 28 days. Melflufen 30 mg i.v. infusion at Day 1 of each cycle Dexamethasone 40 mg p.o. weekly (if ≥75 years 20 mg weekly). Daratumumab 1800 mg s.c. Cycle 1 and 2: Day 1, 8, 15 and 22. Cycle 3 to 6: Day 1 and 15. Cycle 7+: Day 1.

Drug: Melphalan Flufenamide
30 mg intravenous (i.v.) infusion
Other Names:
  • Melflufen

    • Drug: Dexamethasone
    40 mg weekly (if ≥75 years 20 mg weekly). Oral tablets
    Other Names:
  • Dex

    • Drug: Daratumumab
    1800 mg subcutaneous injection
    Other Names:
  • Darzalex

    		•
    Active Comparator: Study Treatment Arm B (daratumumab)

    Treatment will be given in cycles and may be given in an outpatient treatment setting. Each cycle is 28 days. • Daratumumab 1800 mg s.c. Cycle 1 and 2: Day 1, 8, 15 and 22. Cycle 3 to 6: Day 1 and 15. Cycle 7+: Day 1.

    Drug: Daratumumab
    1800 mg subcutaneous injection
    Other Names:
  • Darzalex

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [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

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [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)).

    2. Duration of Response (DOR) [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.

    3. Frequency and Grade of treatment emergent adverse events (TEAE). [13 months]

      Serious Adverse Events will be collected from signing of the Informed Consent until 30 days after last dose of study treatment or initiation of subsequent therapy whichever occurs first. AEs will be collected from the start of study treatment until 30 days after the last dose of any study drug or initiation of subsequent therapy whichever occurs first.

    4. Best Response [12 months]

      proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD or non-evaluable.

    5. Clinical benefit rate (CBR) [12 months]

      the proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR or MR.

    6. Duration of Clinical Benefit (DOCB) [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.

    7. Time to response (TTR) [12 months]

      Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.

    8. Time to progression (TTP) [12 months]

      Time from the date of randomization to the date of the first documented confirmed PD

    9. Time to next treatment (TTNT) [12 months]

      Time from randomization to the date of next anti-myeloma treatment or until death.

    10. Overall survival (OS) [36 months (24 months follow-up after progression)]

      time from date of randomization to death due to any cause

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • A prior diagnosis of multiple myeloma with documented disease progression after last line of therapy

    • Double refractory to an immunomodulatory drug (IMiD) and a Proteasome Inhibitor (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

    • Male and women of childbearing potential agrees to use contraception during the treatment period and during a specified time period 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Multiprofile Hospital for Active Treatment "Sveti Georgi", Plovdiv, Clinical Hematology Clinic Plovdiv Bulgaria
    2 Specialized Hospital for Active Treatment of Hematological Diseases, Clinic of Hematology Sofia Bulgaria
    3 University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology Brno Czechia 62500
    4 University Hospital Hradec Kralove, 4th Internal Clinic of Hematology Kralovice Czechia
    5 University Hospital Ostrava, Clinic of Hematooncology Ostrava Czechia
    6 General University Hospital in Prague, 1st Internal Clinic - Clinic of Hematology Praha Czechia
    7 JSC K. Eristavi National Center of Experimental and Clinical Surgery Tbilisi Georgia
    8 Malkhaz Katsiashvili Multiprofile EMC LTD Tbilisi Georgia
    9 St. Marien-Hospital Siegen gem. GmbH, Dept of Hematology, Medical Oncology and Palliative Medicine Siegen Germany
    10 Alexandra General Hospital, Therapeutic Clinic Athens Greece
    11 General Hospital of Athens "Evangelismos", Department of Hematology and Lymphoma Athens Greece
    12 Oslo University Hospital, Ulleval University Hospital, Oslo Myeloma Center Oslo Norway
    13 Independent Public Healthcare Facility Municipal Hospitals, Teaching Department of Hematology And Prevention of Neoplastic Diseases Chorzów Poland
    14 University Clinical Center in Gdansk, Teaching Department of Hematology and Transplantology Gdańsk Poland
    15 Independent Public Healthcare Facility University Hospital in Krakow, Teaching Unit of the Hematology Department Kraków Poland
    16 Nicolaus Copernicus Provincial Multispecialty Oncology and Traumatology Center in Lodz Lodz Poland
    17 Independent Public Teaching Hospital No.1 in Lublin, Department of Hematooncology, Bone Marrow Transplantation and Chemotherapy Lublin Poland
    18 Leningrad Regional Clinical Hospital Saint Petersburg Russian Federation
    19 V.D. Seredavin Samara Regional Clinical Hospital Samara Russian Federation
    20 Clinical Center of Serbia Belgrade Serbia
    21 Hospital Clinic of Barcelona, Department of Hematology Barcelona Spain
    22 Cherkasy Regional Oncology Dispensary, Regional Treatment and Diagnostic Hematology Center Cherkasy Ukraine
    23 Chernihiv Medical Center of Modern Oncology, Hematology Department Chernihiv Ukraine
    24 City Clinical Hospital No. 4 City Hematology Center Dnipro Ukraine
    25 Kyiv City Clinical Hospital No. 9 Kyiv Ukraine
    26 National Institute of Cancer, Research Department of Hemoblastosis Chemotherapy and Adjuvant Treatment Methods, Department of Oncohematology with Adjuvant Treatment Methods Group Kyiv Ukraine

    Sponsors and Collaborators

    • Oncopeptides AB

    Investigators

    • Principal Investigator: Maria-Victorìa Mateos, MD, PhD, Complejo Hospitalario de Salamanca

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Oncopeptides AB
    ClinicalTrials.gov Identifier:
    NCT04649060
    Other Study ID Numbers:
    • OP-108
    First Posted:
    Dec 2, 2020
    Last Update Posted:
    Mar 4, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Melphalan
    Daratumumab

    Study Results

    No Results Posted as of Mar 4, 2022