NCT04649060 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: TERMINATED
Registry last update: 2023-06-08

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Best Response

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outcome · POSTED

Clinical Benefit Rate (CBR)

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outcome · POSTED

Duration of Clinical Benefit (DOCB)

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outcome · POSTED

Time to Response (TTR)

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outcome · POSTED

Time to Progression (TTP)

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outcome · POSTED

Time to Next Treatment (TTNT)

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outcome · POSTED

Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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 * 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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
intervention Names
Drug: Melflufen
Drug: Dexamethasone
Drug: Daratumumab
label
Arm A (melflufen+dexamethasone+daratumumab)
type
EXPERIMENTAL
description
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
intervention Names
Drug: Daratumumab
label
Arm B (daratumumab)
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A (melflufen+dexamethasone+daratumumab)
description
Powder for solution for i.v. infusion
name
Melflufen
other Names
Melphalan Flufenamide
Pepaxto
Pepaxti
type
DRUG
arm Group Labels
Arm A (melflufen+dexamethasone+daratumumab)
description
Oral tablets
name
Dexamethasone
other Names
Dex
type
DRUG
arm Group Labels
Arm A (melflufen+dexamethasone+daratumumab)
Arm B (daratumumab)
description
Solution for s.c. injection
name
Daratumumab
other Names
Darzalex FASPRO
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: SINGLE
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.
who Masked: OUTCOMES_ASSESSOR

primary Purpose

TREATMENT

Enrollment

count: 54
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Progression Free Survival (PFS)
time Frame
From the date of randomization until the end of study (approximately 12 months).

secondary Outcomes

description
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).
measure
Overall Response Rate (ORR)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
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.
measure
Duration of Response (DOR)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).
measure
Best Response
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.
measure
Clinical Benefit Rate (CBR)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
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.
measure
Duration of Clinical Benefit (DOCB)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.
measure
Time to Response (TTR)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
Time from randomization to the date of the first documented confirmed PD
measure
Time to Progression (TTP)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
Time from randomization to the date of next anti-myeloma treatment or until death.
measure
Time to Next Treatment (TTNT)
time Frame
From the date of randomization until the end of study (approximately 12 months).
description
Time from randomization to death due to any cause.
measure
Overall Survival (OS)
time Frame
From the date of randomization until the end of study (approximately 12 months).

Full study description

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.

Source references

references

citation
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
type
DERIVED
citation
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
type
DERIVED

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice