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Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma (DREAMM 8)

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ClinicalTrials.gov Identifier: NCT04484623
Recruitment Status : Recruiting
First Posted : July 23, 2020
Last Update Posted : July 19, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE July 21, 2020
First Posted Date  ICMJE July 23, 2020
Last Update Posted Date July 19, 2021
Actual Study Start Date  ICMJE October 1, 2020
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2021)
Progression-free survival (PFS) [ Time Frame: Up to 84 months ]
PFS will be defined as the time from start of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.
Original Primary Outcome Measures  ICMJE
 (submitted: July 21, 2020)
Progression-free survival (PFS) [ Time Frame: Up to 84 months ]
Time from start of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2021)
  • Minimal residual disease (MRD) negativity rate [ Time Frame: Up to 84 months ]
    MRD negativity rate will be defined as the percentage of participants who are MRD negative by next-generation sequencing.
  • Overall response rate (ORR) [ Time Frame: Up to 84 months ]
    ORR will be defined as the percentage of participants with a confirmed partial response or better.
  • Complete response rate (CRR) [ Time Frame: Up to 84 months ]
    CRR will be defined as the percentage of participants with a confirmed complete response or better.
  • Very good partial response (VGPR) or better rate [ Time Frame: Up to 84 months ]
    VGPR will be the defined as the percentage of participants with a confirmed VGPR or better.
  • Duration of response (DoR) [ Time Frame: Up to 84 months ]
    DoR will be defined as the time from first documented evidence of partial response or better to date of first documented progression or death, whichever occurs first.
  • Time to best response (TTBR) [ Time Frame: Up to 84 months ]
    TTBR will be defined as the time from the start of study treatment to the first documented evidence of best response among participants who achieve partial response or better.
  • Time to response (TTR) [ Time Frame: Up to 84 months ]
    TTR will be defined as the time from the start of study treatment to the first documented evidence of response among participants who achieve partial response or better.
  • Time to progression (TTP) [ Time Frame: Up to 84 months ]
    TTP will be defined as the time from the start of study treatment until the first documented date of disease progression or death, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Up to 84 months ]
    OS will be defined as the time from randomization to death due to any cause.
  • Progression-free survival on subsequent line of therapy (PFS2) [ Time Frame: Up to 84 months ]
    PFS2 will be defined as the time from start of study treatment to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever occurs first.
  • Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 84 months ]
  • Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [ Time Frame: Up to 84 months ]
  • Number of participants with abnormal ocular findings on ophthalmic examination [ Time Frame: Up to 84 months ]
  • Plasma concentrations of belantamab mafodotin at indicated time points [ Time Frame: Up to 84 months ]
  • Plasma concentrations of total monoclonal antibody (mAb) at indicated time points [ Time Frame: Up to 84 months ]
  • Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points [ Time Frame: Up to 84 months ]
  • Maximum observed concentration (Cmax) for pomalidomide [ Time Frame: Up to 24 hours ]
  • Time of Cmax (Tmax) for pomalidomide [ Time Frame: Up to 24 hours ]
  • 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 ]
  • Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin [ Time Frame: Up to 84 months ]
  • Titers of ADAs against belantamab mafodotin [ Time Frame: Up to 84 months ]
  • 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 ]
    PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.
  • Change from Baseline in impacts as measured by PRO-CTCAE [ Time Frame: Baseline and up to 84 months ]
    PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trial. Impacts of the side effects will be assessed using PRO-CTCAE score.
  • 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 ]
    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.
  • Change from Baseline in HRQoL as measured by EORTC item library 52 (IL52) [ Time Frame: Baseline and up to 84 months ]
    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.
  • Change from Baseline in HRQoL as measured by EORTC QLQ-20-item Multiple Myeloma Module (MY20) [ Time Frame: Baseline and up to 84 months ]
    EORTC QLQ-MY20 is a questionnaire which will evaluate disease symptoms. In EORTC QLQ-MY20, domain scores will be averaged and will be transformed linearly to a score ranging from 0 to 100. Higher score represents high level of symptomatology or problems.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2020)
  • Minimal residual disease (MRD) negativity rate [ Time Frame: Up to 84 months ]
    Percentage of participants who are MRD negative by next-generation sequencing.
  • Overall response rate (ORR) [ Time Frame: Up to 84 months ]
    Percentage of participants with a confirmed partial response or better.
  • Complete response rate (CRR) [ Time Frame: Up to 84 months ]
    Percentage of participants with a confirmed complete response or better.
  • Very good partial response (VGPR) or better rate [ Time Frame: Up to 84 months ]
    Percentage of participants with a confirmed VGPR or better.
  • Duration of response (DoR) [ Time Frame: Up to 84 months ]
    Time from first documented evidence of partial response or better to date of first documented progression or death, whichever occurs first.
  • Time to best response (TTBR) [ Time Frame: Up to 84 months ]
    Time from the start of study treatment to the first documented evidence of best response among participants who achieve partial response or better.
  • Time to response (TTR) [ Time Frame: Up to 84 months ]
    Time from the start of study treatment to the first documented evidence of response among participants who achieve partial response or better.
  • Time to progression (TTP) [ Time Frame: Up to 84 months ]
    Time from the start of study treatment until the first documented date of disease progression or death, whichever occurs first.
  • Overall survival (OS) [ Time Frame: Up to 84 months ]
    Time from randomization to death due to any cause.
  • Progression-free survival on subsequent line of therapy (PFS2) [ Time Frame: Up to 84 months ]
    Time from start of study treatment to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever occurs first.
  • Number of participants with adverse events (AEs) [ Time Frame: Up to 84 months ]
    AEs will be collected.
  • Number of participants with serious adverse events (SAEs) [ Time Frame: Up to 84 months ]
    SAEs will be collected.
  • Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters [ Time Frame: Up to 84 months ]
    Blood and urine samples will be collected for the assessment of hematology, clinical chemistry and urinalysis lab parameters.
  • Number of participants with abnormal ocular findings on ophthalmic examination [ Time Frame: Up to 84 months ]
    Ophthalmic examination will assess abnormal findings.
  • Plasma concentrations of belantamab mafodotin at indicated time points [ Time Frame: Up to 84 months ]
    Plasma concentrations of belantamab mafodotin in Arm A
  • Plasma concentrations of total monoclonal antibody (mAb) at indicated time points [ Time Frame: Up to 84 months ]
    Plasma concentrations of total mAb in Arm A
  • Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points [ Time Frame: Up to 84 months ]
    Plasma concentrations of cys-mcMMAF in Arm A
  • Maximum observed concentration (Cmax) for pomalidomide [ Time Frame: Up to 24 hours ]
    Pharmacokinetic analysis of pomalidomide.
  • Time of Cmax (Tmax) for pomalidomide [ Time Frame: Up to 24 hours ]
    Pharmacokinetic analysis of pomalidomide.
  • 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 ]
    Pharmacokinetic analysis of pomalidomide.
  • Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin [ Time Frame: Up to 84 months ]
    Plasma concentrations of belantamab mafodotin ADAs in Arm A.
  • Titers of ADAs against belantamab mafodotin [ Time Frame: Up to 84 months ]
    Titers of ADAs in Arm A.
  • 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 ]
    PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score.
  • Change from Baseline in impacts as measured by PRO-CTCAE [ Time Frame: Baseline and up to 84 months ]
    PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trial. Impacts of the side effects will be assessed using PRO-CTCAE score.
  • 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 ]
    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.
  • Change from Baseline in HRQoL as measured by EORTC item library 52 (IL52) [ Time Frame: Baseline and up to 84 months ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma
Official Title  ICMJE 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)
Brief Summary 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Belantamab mafodotin
    Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate will be administered.
  • Drug: Pomalidomide
    Immunomodulatory imide drug (IMiD) will be administered.
  • Drug: Dexamethasone
    Synthetic glucocorticoid with anti-tumor activity will be administered.
  • Drug: Bortezomib
    Proteasome Inhibitor will be administered.
Study Arms  ICMJE
  • Experimental: Arm A: Belantamab mafodotin plus Pomalidomide and Dexamethasone
    Interventions:
    • Drug: Belantamab mafodotin
    • Drug: Pomalidomide
    • Drug: Dexamethasone
  • Experimental: Arm B: Bortezomib plus Pomalidomide and Dexamethasone
    Interventions:
    • Drug: Pomalidomide
    • Drug: Dexamethasone
    • Drug: Bortezomib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 21, 2020)
450
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 21, 2027
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 International Myeloma Working Group (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 greater than or equal to (≥)200 milligrams (mg) per 24-hour, or
    2. Serum M-protein concentration ≥0.5 grams/deciliters (g/dL) (≥5.0 g/liter [L]), or
    3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (less than [<]0.26 or greater than [>]1.65) only if participant has no measurable urine or serum M spike.
  • Have undergone autologous stem cell transplant (ASCT) or are considered transplant ineligible. Participants with a history of ASCT are eligible for study participation provided the following eligibility criteria are met: a. ASCT was >100 days prior to the first dose of study medication. b. No active bacterial, viral, or fungal infection(s) present
  • All prior treatment-related toxicities (defined by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0) must be less than or equal to (≤)Grade 1 at the time of enrolment, except for alopecia.
  • Adequate organ system functions as mentioned in the protocol.
  • 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/meter square [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 (NYHA) 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, hypoalbuminemia, esophageal or gastric varices, persistent jaundice.
  • Active infection requiring treatment.
  • Known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria: a. Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/milliliters (mL); b. Cluster of differentiation (CD)4+ T-cell (CD4+) counts >=350 cells/microliters c. No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months.
  • Participants with hepatitis B will be excluded unless the protocol-defined criteria are met.
  • Positive hepatitis C antibody (Hep C Ab) test result or positive hepatitis C ribonucleic acid (Hep C RNA) test result at screening or within 3 months prior to first dose of study treatment, unless the participant can meet the following criteria: a. RNA test negative. b. Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis C virus (HCV) RNA test after a washout period of at least 4 weeks. - 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 peripheral neuropathy with pain within 14 days prior to randomization or ≥Grade 3 peripheral neuropathy.
  • Active or history of venous and arterial 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 laboratory abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • Pregnant or lactating female.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Australia,   Czechia,   France,   Germany,   Greece,   Israel,   Italy,   Korea, Republic of,   New Zealand,   Poland,   Russian Federation,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04484623
Other Study ID Numbers  ICMJE 207499
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP