Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma
Condition: Relapsed Multiple Myeloma; Relapsed-Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Melflufen; Dexamethasone; Daratumumab
Intervention description: Powder for solution for i.v. infusion; Oral tablets; Solution for s.c. injection
Intervention MeSH terms: Dexamethasone; Melphalan; Daratumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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.
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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