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

Oncopeptides

Status and phase: Terminated; Phase 3

Conditions: Relapsed Multiple Myeloma; Relapsed-Refractory Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: Melflufen; Drug: Daratumumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04649060

OP-108

2019-002161-36 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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54 participants in 2 patient groups

Arm A (melflufen+dexamethasone+daratumumab)

Experimental group

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

Treatment:

Drug: Daratumumab

Drug: Dexamethasone

Drug: Melflufen

Arm B (daratumumab)

Active Comparator group

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

Treatment:

Drug: Daratumumab