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A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments (DREAMM-20)

Primary Purpose

Multiple Myeloma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Bela
Belamaf
Lenalidomide
Dexamethasone
Standard of Care
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Bela, Belamaf, Belatamab, Belantamab Mafodotin, Relapsed or Refractory Multiple Myeloma, Transplant-ineligible newly diagnosed multiple myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place. Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG, and measurable disease. PART 1: Participants who have received at least 3 prior lines of anti-myeloma treatments, and have already received an immunomodulating agent, a proteasome inhibitor, and an anti-CD38 mAb (unless contraindicated or unavailable). Lines of therapy are defined by consensus panel of the International Myeloma Workshop. PART 2: Participants who meet all of the following: Have undergone Autologous stem cell transplant (ASCT) or are considered transplant ineligible Have been previously treated with at least ONE prior line of MM therapy Have documented disease progression during or after their most recent therapy PART 3: Participants who meet both of the following: NDMM with a requirement for treatment as documented per IMWG criteria Not considered a candidate for high dose chemotherapy with ASCT due to: Age ≥ 65 years OR Age 18-65 years with presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT or who refuse high-dose chemotherapy with ASCT as an initial treatment. Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol. Exclusion Criteria: Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia. 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 with study procedures. Active infection requiring antibiotic, antiviral, or antifungal treatment. Known, current drug or alcohol abuse. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by chair or designee) is allowing exception to this criterion for a specific participant.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Part 1 - Dose Escalation Phase in Participants with RRMM

    Part 2 - Combination Treatments in Participants with RRMM

    Part 3 - Combination Treatments in Participants with TI-NDMM

    Arm Description

    Bela will be administered in participants with RRMM until progressive disease (PD). Participants may switch to Belamaf in case of PD.

    Participants with RRMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.

    Participants with TI-NDMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.

    Outcomes

    Primary Outcome Measures

    Part 1, 2 and 3: Number of Participants with any Adverse Event
    Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
    Part 1, 2 and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters
    Part 2 and 3: Number of Participants with Corneal Adverse Events (CAEs)

    Secondary Outcome Measures

    Part 1, 2 and 3: Observed Plasma Concentration of Bela
    Part 1, 2 and 3: Area Under the Curve (AUC) of Bela
    Part 1, 2 and 3: Maximum Concentration (Cmax) of Bela
    Part 1, 2 and 3: Number of Participants with Anti-Drug Antibodies (ADA) against Bela
    Part 1, 2 and 3: Titers of ADA against Bela
    Part 2 and 3: Number of Participants with ADAs against Belamaf
    Part 2 and 3: Titers of ADAs against Belamaf
    Part 1, 2 and 3: Objective Response Rate (ORR)
    ORR is defined as the percentage of participants with a confirmed Partial Response (PR) or better [i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR), Stringent Complete Response (sCR)] as per International Myeloma Working Group (IMWG) criteria.
    Part 2 and 3: Stringent Complete Response (sCR) Rate
    sCR is defined as the percentage of participants with CR plus normal free light chain ratio and absence of clonal cells in the bone marrow (BM) as per IMWG criteria.
    Part 2 and 3: Complete Response (CR) Rate
    CR rate is defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR) as per IMWG criteria.
    Part 2 and 3: Very Good Partial Response (VGPR) Rate
    VGPR rate is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, sCR) as per IMWG criteria.
    Part 2 and 3: Observed Plasma Concentration of Belamaf

    Full Information

    First Posted
    January 27, 2023
    Last Updated
    January 27, 2023
    Sponsor
    GlaxoSmithKline
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05714839
    Brief Title
    A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments
    Acronym
    DREAMM-20
    Official Title
    A Phase 1/2 Open-label, Multicentre, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Clinical Activity of Belantamab as Monotherapy and in Combination With Other Treatments in Participants With Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    February 28, 2023 (Anticipated)
    Primary Completion Date
    June 28, 2027 (Anticipated)
    Study Completion Date
    June 28, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    GlaxoSmithKline

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The study consists of three parts Part 1: The primary purpose of this part is to determine the safety, and recommended part 2 dose of belantamab (bela) in participants with relapsed or refractory multiple myeloma (RRMM). Part 2: The primary purpose of this part is to determine safety, tolerability and percentage of adverse events (AEs) that happen to eyes in participants with RRMM treated with bela in combination with other treatments. Part 3: The primary objective of this part is to assess the safety, tolerability and rate of ocular AEs in participants with transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) treated with either belantamab mafodotin (belamaf) or bela in combination with other treatments.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Multiple Myeloma
    Keywords
    Bela, Belamaf, Belatamab, Belantamab Mafodotin, Relapsed or Refractory Multiple Myeloma, Transplant-ineligible newly diagnosed multiple myeloma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    124 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Part 1 - Dose Escalation Phase in Participants with RRMM
    Arm Type
    Experimental
    Arm Description
    Bela will be administered in participants with RRMM until progressive disease (PD). Participants may switch to Belamaf in case of PD.
    Arm Title
    Part 2 - Combination Treatments in Participants with RRMM
    Arm Type
    Experimental
    Arm Description
    Participants with RRMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.
    Arm Title
    Part 3 - Combination Treatments in Participants with TI-NDMM
    Arm Type
    Experimental
    Arm Description
    Participants with TI-NDMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.
    Intervention Type
    Drug
    Intervention Name(s)
    Bela
    Other Intervention Name(s)
    Belantamab, GSK2857914
    Intervention Description
    Bela will be administered.
    Intervention Type
    Drug
    Intervention Name(s)
    Belamaf
    Other Intervention Name(s)
    Belantamab mafodotin, GSK2857916 BLENREP
    Intervention Description
    Belamaf will be administered.
    Intervention Type
    Drug
    Intervention Name(s)
    Lenalidomide
    Intervention Description
    Lenalidomide will be administered.
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone
    Intervention Description
    Dexamethasone will be administered.
    Intervention Type
    Drug
    Intervention Name(s)
    Standard of Care
    Intervention Description
    Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered
    Primary Outcome Measure Information:
    Title
    Part 1, 2 and 3: Number of Participants with any Adverse Event
    Time Frame
    Up to 52 months
    Title
    Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
    Time Frame
    Cycle 1 (Each cycle is of 28 days)
    Title
    Part 1, 2 and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Number of Participants with Corneal Adverse Events (CAEs)
    Time Frame
    Up to 52 months
    Secondary Outcome Measure Information:
    Title
    Part 1, 2 and 3: Observed Plasma Concentration of Bela
    Time Frame
    Up to 52 months
    Title
    Part 1, 2 and 3: Area Under the Curve (AUC) of Bela
    Time Frame
    Up to 52 months
    Title
    Part 1, 2 and 3: Maximum Concentration (Cmax) of Bela
    Time Frame
    Up to 52 months
    Title
    Part 1, 2 and 3: Number of Participants with Anti-Drug Antibodies (ADA) against Bela
    Time Frame
    Up to 52 months
    Title
    Part 1, 2 and 3: Titers of ADA against Bela
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Number of Participants with ADAs against Belamaf
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Titers of ADAs against Belamaf
    Time Frame
    Up to 52 months
    Title
    Part 1, 2 and 3: Objective Response Rate (ORR)
    Description
    ORR is defined as the percentage of participants with a confirmed Partial Response (PR) or better [i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR), Stringent Complete Response (sCR)] as per International Myeloma Working Group (IMWG) criteria.
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Stringent Complete Response (sCR) Rate
    Description
    sCR is defined as the percentage of participants with CR plus normal free light chain ratio and absence of clonal cells in the bone marrow (BM) as per IMWG criteria.
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Complete Response (CR) Rate
    Description
    CR rate is defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR) as per IMWG criteria.
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Very Good Partial Response (VGPR) Rate
    Description
    VGPR rate is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, sCR) as per IMWG criteria.
    Time Frame
    Up to 52 months
    Title
    Part 2 and 3: Observed Plasma Concentration of Belamaf
    Time Frame
    Up to 52 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place. Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG, and measurable disease. PART 1: Participants who have received at least 3 prior lines of anti-myeloma treatments, and have already received an immunomodulating agent, a proteasome inhibitor, and an anti-CD38 mAb (unless contraindicated or unavailable). Lines of therapy are defined by consensus panel of the International Myeloma Workshop. PART 2: Participants who meet all of the following: Have undergone Autologous stem cell transplant (ASCT) or are considered transplant ineligible Have been previously treated with at least ONE prior line of MM therapy Have documented disease progression during or after their most recent therapy PART 3: Participants who meet both of the following: NDMM with a requirement for treatment as documented per IMWG criteria Not considered a candidate for high dose chemotherapy with ASCT due to: Age ≥ 65 years OR Age 18-65 years with presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT or who refuse high-dose chemotherapy with ASCT as an initial treatment. Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol. Exclusion Criteria: Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia. 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 with study procedures. Active infection requiring antibiotic, antiviral, or antifungal treatment. Known, current drug or alcohol abuse. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by chair or designee) is allowing exception to this criterion for a specific participant.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    US GSK Clinical Trials Call Center
    Phone
    877-379-3718
    Email
    GSKClinicalSupportHD@gsk.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    EU GSK Clinical Trials Call Center
    Phone
    +44 (0) 20 89904466
    Email
    GSKClinicalSupportHD@gsk.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    GSK Clinical Trials
    Organizational Affiliation
    GlaxoSmithKline
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
    IPD Sharing Time Frame
    Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
    IPD Sharing Access Criteria
    Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
    IPD Sharing URL
    https://www.gsk.com/en-gb/innovation/trials/data-transparency/

    Learn more about this trial

    A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments

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