Clinical Trials /

Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma

NCT04484623

Description:

This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma
  • Official Title: A Phase III, Multicenter, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Pomalidomide and Dexamethasone (B-Pd) Versus Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Participants With Relapsed/Refractory Multiple Myeloma (DREAMM 8)

Clinical Trial IDs

  • ORG STUDY ID: 207499
  • NCT ID: NCT04484623

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinArm A:Belantamab mafodotin plus Pomalidomide and Dexamethasone
PomalidomideArm A:Belantamab mafodotin plus Pomalidomide and Dexamethasone
DexamethasoneArm A:Belantamab mafodotin plus Pomalidomide and Dexamethasone
BortezomibArm B:Bortezomib plus Pomalidomide and Dexamethasone

Purpose

This study will evaluate the efficacy and safety of belantamab mafodotin in combination with pomalidomide and dexamethasone (Arm A) compared with that of combination of pomalidomide, bortezomib and dexamethasone (Arm B) in participants with relapsed/refractory multiple myeloma (RRMM).

Trial Arms

NameTypeDescriptionInterventions
Arm A:Belantamab mafodotin plus Pomalidomide and DexamethasoneExperimental
  • Belantamab mafodotin
  • Pomalidomide
  • Dexamethasone
Arm B:Bortezomib plus Pomalidomide and DexamethasoneExperimental
  • Pomalidomide
  • Dexamethasone
  • Bortezomib

Eligibility Criteria

        Inclusion Criteria:

          -  Capable of giving signed informed consent.

          -  Male or female, 18 years or older.

          -  Have a confirmed diagnosis of multiple myeloma (MM) as defined by the IMWG criteria.

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

          -  Have been previously treated with at least 1 prior line of MM therapy including a
             lenalidomide-containing regimen and must have documented disease progression during or
             after their most recent therapy.

          -  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, or

               3. Serum free light chain (FLC) assay: involved FLC level >=10 mg per deciliter and
                  an abnormal serum free light chain ratio (<0.26 or >1.65) only if participant has
                  no measurable urine or serum M spike.

          -  Have undergone autologous stem cell transplant (SCT) or are considered transplant
             ineligible. Participants with a history of autologous SCT may be eligible for study
             participation.

          -  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 enrolment, except for alopecia.

          -  Adequate organ system functions.

          -  Male and female participants agree to abide by protocol-defined contraceptive
             requirements.

        Exclusion Criteria:

          -  Active plasma cell leukemia, symptomatic amyloidosis or active polyneuropathy,
             organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, and skin
             changes (POEMS) syndrome at the time of screening.

          -  Prior allogeneic SCT.

          -  Systemic anti-myeloma therapy (including chemotherapy and systemic steroids) within 14
             days or five half-lives (whichever is shorter) preceding the first dose of study drug;
             prior treatment with a monoclonal antibody drug within 30 days of receiving the first
             dose of study drugs.

          -  Plasmapheresis within 7 days prior to the first dose of study drug.

          -  Received prior treatment with or intolerant to pomalidomide.

          -  Received prior Beta cell maturation antigen (BCMA) targeted therapy.

          -  Intolerant to bortezomib or refractory to bortezomib (for example; participant
             experienced progressive disease during treatment, or within 60 days of completing
             treatment, with a bortezomib-containing regimen of 1.3 mg/ m^2 twice weekly).

          -  Evidence of cardiovascular risk including any of the following;

               1. Evidence of current clinically significant untreated arrhythmias, including
                  clinically significant electrocardiogram abnormalities including second degree
                  (Mobitz type II) or third degree atrioventricular (AV) block.

               2. Recent history within (3 months of screening) of myocardial infarction, acute
                  coronary syndromes (including unstable angina), coronary angioplasty, or stenting
                  or bypass grafting .

               3. Class III or IV heart failure as defined by the New York Heart Association
                  functional classification system

               4. Uncontrolled hypertension.

          -  Any major surgery within the last 4 weeks.

          -  Previous or concurrent invasive malignancy other than multiple myeloma, except:

               1. The disease must be considered medically stable for at least 2 years; or

               2. The participant must not be receiving active therapy, other than hormonal therapy
                  for this disease.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to
             belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of
             the components of the study treatment.

          -  Evidence of active mucosal or internal bleeding.

          -  Cirrhosis or current unstable liver or biliary disease per investigator assessment
             defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia,
             oesophageal or gastric varices, persistent jaundice.

          -  Active infection requiring treatment.

          -  Known human immunodeficiency virus (HIV) infection.

          -  Presence of hepatitis B surface antigen (HbsAg), or hepatitis B core antibody (HbcAb)
             at screening or within 3 months prior to first dose of study treatment.

          -  Positive hepatitis C antibody test result or positive hepatitis ribonucleic acid test
             result at screening or within 3 months prior to first dose of study treatment.

          -  Intolerance or contraindications to anti-viral prophylaxis.

          -  Presence of active renal conditions (such as infection, severe renal impairment
             requiring dialysis or any other condition that could affect participant's safety).

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

          -  Active or history of venous thromboembolism within the past 3 months.

          -  Contraindications to or unwilling to undergo protocol-required anti-thrombotic
             prophylaxis.

          -  Current corneal disease except for mild punctate keratopathy.

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder or other
             conditions (including lab abnormalities) that could interfere with participant's
             safety, obtaining informed consent or compliance to the study procedures.

          -  Pregnant or lactating female.
      
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:Up to 84 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:Minimal residual disease (MRD) negativity rate
Time Frame:Up to 84 months
Safety Issue:
Description:Percentage of participants who are MRD negative by next-generation sequencing.
Measure:Overall response rate (ORR)
Time Frame:Up to 84 months
Safety Issue:
Description:Percentage of participants with a confirmed partial response or better.
Measure:Complete response rate (CRR)
Time Frame:Up to 84 months
Safety Issue:
Description:Percentage of participants with a confirmed complete response or better.
Measure:Very good partial response (VGPR) or better rate
Time Frame:Up to 84 months
Safety Issue:
Description:Percentage of participants with a confirmed VGPR or better.
Measure:Duration of response (DoR)
Time Frame:Up to 84 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 best response (TTBR)
Time Frame:Up to 84 months
Safety Issue:
Description:Time from the start of study treatment to the first documented evidence of best response among participants who achieve partial response or better.
Measure:Time to response (TTR)
Time Frame:Up to 84 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)
Time Frame:Up to 84 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 84 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 84 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:Number of participants with adverse events (AEs)
Time Frame:Up to 84 months
Safety Issue:
Description:AEs will be collected.
Measure:Number of participants with serious adverse events (SAEs)
Time Frame:Up to 84 months
Safety Issue:
Description:SAEs will be collected.
Measure:Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters
Time Frame:Up to 84 months
Safety Issue:
Description:Blood and urine samples will be collected for the assessment of hematology, clinical chemistry and urinalysis lab parameters.
Measure:Number of participants with abnormal ocular findings on ophthalmic examination
Time Frame:Up to 84 months
Safety Issue:
Description:Ophthalmic examination will assess abnormal findings.
Measure:Plasma concentrations of belantamab mafodotin at indicated time points
Time Frame:Up to 84 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 84 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 84 months
Safety Issue:
Description:Plasma concentrations of cys-mcMMAF in Arm A
Measure:Maximum observed concentration (Cmax) for pomalidomide
Time Frame:Up to 24 hours
Safety Issue:
Description:Pharmacokinetic analysis of pomalidomide.
Measure:Time of Cmax (Tmax) for pomalidomide
Time Frame:Up to 24 hours
Safety Issue:
Description:Pharmacokinetic analysis of pomalidomide.
Measure:Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC[0-t]) for pomalidomide
Time Frame:Up to 24 hours
Safety Issue:
Description:Pharmacokinetic analysis of pomalidomide.
Measure:Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin
Time Frame:Up to 84 months
Safety Issue:
Description:Plasma concentrations of belantamab mafodotin ADAs in Arm A.
Measure:Titers of ADAs against belantamab mafodotin
Time Frame:Up to 84 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 terminology criteria for adverse events (PRO-CTCAE)
Time Frame:Baseline and up to 84 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 84 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 84 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 item library 52 (IL52)
Time Frame:Baseline and up to 84 months
Safety Issue:
Description:EORTC QLQ- 20-item Multiple Myeloma Module (MY20) questionnaire will be referred to as the EORTC IL52. Only disease symptoms domain will be assessed. 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
  • Pomalidomide
  • Dexamethasone
  • Bortezomib

Last Updated

October 20, 2020