Clinical Trials /

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

NCT04649060

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Melphalan Flufenamide (Melflufen) in Combination With Daratumumab in Relapsed Refractory Multiple Myeloma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: OP-108
  • NCT ID: NCT04649060

Conditions

  • Relapse Multiple Myeloma
  • Multiple Myeloma

Interventions

DrugSynonymsArms
Melphalan FlufenamideMelflufenStudy Treatment Arm A (melflufen+dexamethasone+daratumumab)
DexamethasoneDexStudy Treatment Arm A (melflufen+dexamethasone+daratumumab)
DaratumumabDarzalexStudy Treatment Arm A (melflufen+dexamethasone+daratumumab)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Study Treatment Arm A (melflufen+dexamethasone+daratumumab)ExperimentalTreatment will be given in cycles and may be given in an outpatient treatment setting. Each cycle is 28 days. Melflufen 30 mg i.v. infusion at Day 1 of each cycle Dexamethasone 40 mg p.o. weekly (if ≥75 years 20 mg weekly). 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.
  • Melphalan Flufenamide
  • Dexamethasone
  • Daratumumab
Study Treatment Arm B (daratumumab)Active ComparatorTreatment 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.
  • Daratumumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:12 months
Safety Issue:
Description: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

Measure:Overall Response Rate (ORR)
Time Frame:12 months
Safety Issue:
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:Duration of Response (DOR)
Time Frame:12 months
Safety Issue:
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:Frequency and Grade of treatment emergent adverse events (TEAE).
Time Frame:13 months
Safety Issue:
Description: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.
Measure:Best Response
Time Frame:12 months
Safety Issue:
Description:proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD or non-evaluable.
Measure:Clinical benefit rate (CBR)
Time Frame:12 months
Safety Issue:
Description:the proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR or MR.
Measure:Duration of Clinical Benefit (DOCB)
Time Frame:12 months
Safety Issue:
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:Time to response (TTR)
Time Frame:12 months
Safety Issue:
Description:Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.
Measure:Time to progression (TTP)
Time Frame:12 months
Safety Issue:
Description:Time from the date of randomization to the date of the first documented confirmed PD
Measure:Time to next treatment (TTNT)
Time Frame:12 months
Safety Issue:
Description:Time from randomization to the date of next anti-myeloma treatment or until death.
Measure:Overall survival (OS)
Time Frame:36 months (24 months follow-up after progression)
Safety Issue:
Description:time from date of randomization to death due to any cause

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Oncopeptides AB

Last Updated

July 12, 2021