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

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ClinicalTrials.gov Identifier: NCT04649060
Recruitment Status : Recruiting
First Posted : December 2, 2020
Last Update Posted : January 26, 2021
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB

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
Relapse Multiple Myeloma Multiple Myeloma Drug: Melphalan Flufenamide Drug: Dexamethasone Drug: Daratumumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 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 : December 7, 2020
Estimated Primary Completion Date : June 15, 2023
Estimated Study Completion Date : November 15, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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 Name: Melflufen

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

Drug: Daratumumab
1800 mg subcutaneous injection
Other Name: 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 Name: Darzalex




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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). [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 12 months ]
    Time from the date of randomization to the date of the first documented confirmed PD

  9. Time to next treatment (TTNT) [ Time Frame: 12 months ]
    Time from randomization to the date of next anti-myeloma treatment or until death.

  10. Overall survival (OS) [ Time Frame: 36 months (24 months follow-up after progression) ]
    time from date of randomization to death due to any cause



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04649060


Contacts
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Contact: VP Chief Operating Officer +4686152040 trials@oncopeptides.se

Locations
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Czechia
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology Recruiting
Brno, Czechia, 62500
Contact: Pour         
Principal Investigator: Ludek Pour         
University Hospital Hradec Kralove, 4th Internal Clinic of Hematology Recruiting
Kralovice, Czechia
Principal Investigator: Vladimir Maisnar         
Sponsors and Collaborators
Oncopeptides AB
Investigators
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Principal Investigator: Maria-Victorìa Mateos, MD, PhD Complejo Hospitalario de Salamanca
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Responsible Party: Oncopeptides AB
ClinicalTrials.gov Identifier: NCT04649060    
Other Study ID Numbers: OP-108
First Posted: December 2, 2020    Key Record Dates
Last Update Posted: January 26, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Melphalan
Daratumumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents