Study of Melflufen (Melphalan Flufenamide) 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 due to financial issues following an FDA request for a partial clinical hold.)
First Posted : December 2, 2020
Results First Posted : June 8, 2023
Last Update Posted : June 8, 2023
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Sponsor:
Oncopeptides AB
Information provided by (Responsible Party):
Oncopeptides AB
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed Multiple Myeloma Relapsed-Refractory Multiple Myeloma | Drug: Melflufen 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 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. |
| 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 21, 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: Arm A (melflufen+dexamethasone+daratumumab)
Treatment was given in 28-day cycles in an outpatient treatment setting.
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Drug: Melflufen
Powder for solution for i.v. infusion
Other Names:
Drug: Dexamethasone Oral tablets
Other Name: Dex Drug: Daratumumab Solution for s.c. injection
Other Name: Darzalex FASPRO |
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Active Comparator: 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 |
Drug: Daratumumab
Solution for s.c. injection
Other Name: Darzalex FASPRO |
Primary Outcome Measures :
- Progression Free Survival (PFS) [ Time Frame: From the date of randomization until the end of study (approximately 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, whichever occurred first.
Secondary Outcome Measures :
- Overall Response Rate (ORR) [ Time Frame: From the date of randomization until the end of study (approximately 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: From the date of randomization until the end of study (approximately 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.
- Best Response [ Time Frame: From the date of randomization until the end of study (approximately 12 months). ]Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).
- Clinical Benefit Rate (CBR) [ Time Frame: From the date of randomization until the end of study (approximately 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: From the date of randomization until the end of study (approximately 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: From the date of randomization until the end of study (approximately 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: From the date of randomization until the end of study (approximately 12 months). ]Time from randomization to the date of the first documented confirmed PD
- Time to Next Treatment (TTNT) [ Time Frame: From the date of randomization until the end of study (approximately 12 months). ]Time from randomization to the date of next anti-myeloma treatment or until death.
- Overall Survival (OS) [ Time Frame: From the date of randomization until the end of study (approximately 12 months). ]Time from 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 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
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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
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 |
Study Documents (Full-Text)
Documents provided by Oncopeptides AB:
Documents provided by Oncopeptides AB:
Study Protocol [PDF] November 25, 2020
Statistical Analysis Plan [PDF] May 11, 2022
| Responsible Party: | Oncopeptides AB |
| ClinicalTrials.gov Identifier: | NCT04649060 |
| Other Study ID Numbers: |
OP-108 2019-002161-36 ( EudraCT Number ) |
| First Posted: | December 2, 2020 Key Record Dates |
| Results First Posted: | June 8, 2023 |
| Last Update Posted: | June 8, 2023 |
| Last Verified: | February 2023 |
| 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 |