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Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma

NCT04246047

Description:

This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (Arm A) versus daratumumab in combination with bortezomib/dexamethasone (Arm B) in the participants with relapsed recurrent multiple myeloma.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of Efficacy and Safety of Belantamab Mafodotin, Bortezomib and Dexamethasone Versus Daratumumab, Bortezomib and Dexamethasone in Participants With Relapsed/Refractory Multiple Myeloma
  • Official Title: DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (B-Vd) Compared With the Combination of Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants With Relapsed/Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 207503
  • NCT ID: NCT04246047

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinBelantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)
DaratumumabDaratumumab and Bortezomib plus Dexamethasone (Arm B)
BortezomibBelantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)
DexamethasoneBelantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)

Purpose

This is a Phase 3, randomized, open-label study designed to evaluate safety and efficacy of belantamab mafodotin in combination with bortezomib/dexamethasone (Arm A) versus daratumumab in combination with bortezomib/dexamethasone (Arm B) in the participants with relapsed recurrent multiple myeloma.

Detailed Description

      Approximately 478 participants will be randomized 1:1 to Arm A (B-Vd) or Arm B (D-Vd).
      Treatment will continue in both arms until progressive disease, death, unacceptable toxicity,
      withdrawal of consent or end of study, whichever occurs first.
    

Trial Arms

NameTypeDescriptionInterventions
Belantamab mafodotin and Bortezomib plus Dexamethasone (Arm A)Experimental
  • Belantamab mafodotin
  • Bortezomib
  • Dexamethasone
Daratumumab and Bortezomib plus Dexamethasone (Arm B)Active Comparator
  • Daratumumab
  • Bortezomib
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Confirmed diagnosis of multiple myeloma as defined by the International Myeloma
             Working Group (IMWG) criteria.

          -  Previously treated with at least 1 prior line of multiple myeloma (MM) therapy, and
             must have documented disease progression during or after their most recent therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          -  Must have at least 1 aspect of measurable disease, defined as one of the following;

               1. Urine M-protein excretion >=200 mg per 24-hour, or

               2. Serum M-protein concentration >=0.5 grams per deciliter (g/dL), or

               3. Serum free light chain (FLC) assay: involved FLC level >=10 mg per dL (>=100 mg
                  per liter) and an abnormal serum free light chain ratio (<0.26 or >1.65).

          -  All prior treatment-related toxicities (defined by National Cancer Institute Common
             Toxicity Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be <=Grade 1 at the
             time of enrollment, except for alopecia.

          -  Adequate organ function

        Exclusion Criteria:

          -  Intolerant to daratumumab.

          -  Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive
             disease during treatment with anti-CD38 therapy, or within 60 days of completing that
             treatment).

          -  Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease
             during treatment with a bortezomib-containing regimen of 1.3 mg/m^2 twice weekly, or
             within 60 days of completing that treatment). Note: participants with progressive
             disease during treatment with a weekly bortezomib regimen are allowed.

          -  Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain.

          -  Prior treatment with anti-B-cell maturation antigen (anti-BCMA) therapy.

          -  Prior allogenic stem cell transplant.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder or other
             conditions, including renal, liver, cardiovascular, or certain prior malignancies.

          -  Corneal epithelial disease.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to an average of 34 months
Safety Issue:
Description:Time from start of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Measure:Complete response rate (CRR)
Time Frame:Up to 74 months
Safety Issue:
Description:Percentage of participants with a confirmed complete response or better.
Measure:Overall response rate (ORR)
Time Frame:Up to 74 months
Safety Issue:
Description:Percentage of participants with a confirmed partial response or better.
Measure:Duration of response (DoR) after administration of study treatment
Time Frame:Up to 74 months
Safety Issue:
Description:Time from first documented evidence of partial response or better to date of first documented progression or death, whichever occurs first.
Measure:Time to response (TTR) after administration of study treatment
Time Frame:Up to 74 months
Safety Issue:
Description:Time from the start of study treatment to the first documented evidence of response among participants who achieve partial response or better.
Measure:Time to Progression (TTP) after administration of study treatment
Time Frame:Up to 74 months
Safety Issue:
Description:Time from the start of study treatment until the first documented date of disease progression or death, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:Up to 74 months
Safety Issue:
Description:Time from randomization to death due to any cause.
Measure:Progression-free survival on subsequent line of therapy (PFS2)
Time Frame:Up to 74 months
Safety Issue:
Description:Time from start of study treatment to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever occurs first.
Measure:Minimal Residual Disease (MRD) negativity rate after administration of study treatment
Time Frame:Up to 74 months
Safety Issue:
Description:Percentage of participants who are MRD negative by next-generation sequencing.
Measure:Number of participants with adverse events (AEs)
Time Frame:Up to 74 months
Safety Issue:
Description:AEs will be collected, including abnormal laboratory parameters.
Measure:Number of participants with serious adverse events (SAEs)
Time Frame:Up to 74 months
Safety Issue:
Description:SAEs will be collected.
Measure:Number of participants with abnormal ocular findings on ophthalmic examination
Time Frame:Up to 74 months
Safety Issue:
Description:Ophthalmic examination will assess abnormal findings.
Measure:Plasma concentrations of belantamab mafodotin at indicated time points
Time Frame:Up to 74 months
Safety Issue:
Description:Plasma concentrations of belantamab mafodotin in Arm A.
Measure:Plasma concentrations of total monoclonal antibody (mAb) at indicated time points
Time Frame:Up to 74 months
Safety Issue:
Description:Plasma concentrations of total mAb in Arm A.
Measure:Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points
Time Frame:Up to 74 months
Safety Issue:
Description:Plasma concentrations of cys-mcMMAF in Arm A.
Measure:Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin
Time Frame:Up to 74 months
Safety Issue:
Description:Plasma concentrations of belantamab mafodotin ADAs in Arm A.
Measure:Titers of ADAs against belantamab mafodotin
Time Frame:Up to 74 months
Safety Issue:
Description:Titers of ADAs in Arm A.
Measure:Change from Baseline in symptoms as measured by Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events (PRO-CTCAE)
Time Frame:Baseline and Up to 74 months
Safety Issue:
Description:PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score.
Measure:Change from Baseline in impacts as measured by PRO-CTCAE
Time Frame:Baseline and Up to 74 months
Safety Issue:
Description:PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trial. Impacts of the side effects will be assessed using PRO-CTCAE score.
Measure:Change from Baseline in health related quality of life (HRQoL) as measured by European Organization for Research and Treatment of Cancer Quality of life Questionnaire 30-item core module (EORTC QLQ-C30)
Time Frame:Baseline and Up to 74 months
Safety Issue:
Description:EORTC Quality of Life questionnaire QLQ-C30 on a scale of 0-100. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life.
Measure:Change from Baseline in HRQoL as measured by EORTC, 20-Item Multiple Myeloma Module (QLQ-MY20)
Time Frame:Baseline and Up to 74 months
Safety Issue:
Description:EORTC 20-item Multiple Myeloma Module QLQ-MY20 questionnaire: only Disease Symptoms Domain will be administered. A high score represents a high level of symptoms or problems.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Belantamab mafodotin
  • Relapsed/refractory multiple myeloma
  • Daratumumab
  • Bortezomib
  • Dexamethasone

Last Updated

August 6, 2020