Study of Melphalan Flufenamide (Melflufen) in Combination With Daratumumab in Relapsed Refractory Multiple Myeloma (LIGHTHOUSE)
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| ClinicalTrials.gov Identifier: NCT04649060 |
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Recruitment Status :
Terminated
(The sponsor decided to terminate the study following an FDA request of a partial clinical hold.)
First Posted : December 2, 2020
Last Update Posted : March 4, 2022
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Sponsor:
Oncopeptides AB
Information provided by (Responsible Party):
Oncopeptides AB
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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 |
| Study Type : | Interventional (Clinical Trial) |
| 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 : | December 7, 2020 |
| Actual Primary Completion Date : | February 7, 2022 |
| Actual Study Completion Date : | February 7, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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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 :
- 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 :
- 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)).
- 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.
- 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.
- Best Response [ Time Frame: 12 months ]proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD or non-evaluable.
- 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.
- 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.
- 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.
- Time to progression (TTP) [ Time Frame: 12 months ]Time from the date of randomization to the date of the first documented confirmed PD
- Time to next treatment (TTNT) [ Time Frame: 12 months ]Time from randomization to the date of next anti-myeloma treatment or until death.
- Overall survival (OS) [ Time Frame: 36 months (24 months follow-up after progression) ]time from date of randomization to death due to any cause
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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
Locations
Show 26 study locations
Sponsors and Collaborators
Oncopeptides AB
Investigators
| Principal Investigator: | Maria-Victorìa Mateos, MD, PhD | Complejo Hospitalario de Salamanca |
| 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: | March 4, 2022 |
| Last Verified: | February 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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:
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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 |