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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04484623




Registration number
NCT04484623
Ethics application status
Date submitted
21/07/2020
Date registered
23/07/2020
Date last updated
19/04/2021

Titles & IDs
Public title
Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myeloma
Scientific 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)
Secondary ID [1] 0 0
207499
Universal Trial Number (UTN)
Trial acronym
DREAMM 8
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Belantamab mafodotin
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Bortezomib

Experimental: Arm A:Belantamab mafodotin plus Pomalidomide and Dexamethasone -

Experimental: Arm B:Bortezomib plus Pomalidomide and Dexamethasone -


Treatment: Drugs: Belantamab mafodotin
Humanized anti-B-cell maturation antigen (BCMA) antibody/drug conjugate

Treatment: Drugs: Pomalidomide
Immunomodulatory imide drug (IMiD)

Treatment: Drugs: Dexamethasone
Synthetic glucocorticoid with anti-tumor activity

Treatment: Drugs: Bortezomib
Proteasome Inhibitor

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) - Time from start of study treatment to the first documented disease progression or death due to any cause, whichever occurs first.
Timepoint [1] 0 0
Up to 84 months
Secondary outcome [1] 0 0
Minimal residual disease (MRD) negativity rate - Percentage of participants who are MRD negative by next-generation sequencing.
Timepoint [1] 0 0
Up to 84 months
Secondary outcome [2] 0 0
Overall response rate (ORR) - Percentage of participants with a confirmed partial response or better.
Timepoint [2] 0 0
Up to 84 months
Secondary outcome [3] 0 0
Complete response rate (CRR) - Percentage of participants with a confirmed complete response or better.
Timepoint [3] 0 0
Up to 84 months
Secondary outcome [4] 0 0
Very good partial response (VGPR) or better rate - Percentage of participants with a confirmed VGPR or better.
Timepoint [4] 0 0
Up to 84 months
Secondary outcome [5] 0 0
Duration of response (DoR) - Time from first documented evidence of partial response or better to date of first documented progression or death, whichever occurs first.
Timepoint [5] 0 0
Up to 84 months
Secondary outcome [6] 0 0
Time to best response (TTBR) - Time from the start of study treatment to the first documented evidence of best response among participants who achieve partial response or better.
Timepoint [6] 0 0
Up to 84 months
Secondary outcome [7] 0 0
Time to response (TTR) - Time from the start of study treatment to the first documented evidence of response among participants who achieve partial response or better.
Timepoint [7] 0 0
Up to 84 months
Secondary outcome [8] 0 0
Time to progression (TTP) - Time from the start of study treatment until the first documented date of disease progression or death, whichever occurs first.
Timepoint [8] 0 0
Up to 84 months
Secondary outcome [9] 0 0
Overall survival (OS) - Time from randomization to death due to any cause.
Timepoint [9] 0 0
Up to 84 months
Secondary outcome [10] 0 0
Progression-free survival on subsequent line of therapy (PFS2) - Time from start of study treatment to disease progression after initiation of new anti-cancer therapy or death from any cause, whichever occurs first.
Timepoint [10] 0 0
Up to 84 months
Secondary outcome [11] 0 0
Number of participants with adverse events (AEs) - AEs will be collected.
Timepoint [11] 0 0
Up to 84 months
Secondary outcome [12] 0 0
Number of participants with serious adverse events (SAEs) - SAEs will be collected.
Timepoint [12] 0 0
Up to 84 months
Secondary outcome [13] 0 0
Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters - Blood and urine samples will be collected for the assessment of hematology, clinical chemistry and urinalysis lab parameters.
Timepoint [13] 0 0
Up to 84 months
Secondary outcome [14] 0 0
Number of participants with abnormal ocular findings on ophthalmic examination - Ophthalmic examination will assess abnormal findings.
Timepoint [14] 0 0
Up to 84 months
Secondary outcome [15] 0 0
Plasma concentrations of belantamab mafodotin at indicated time points - Plasma concentrations of belantamab mafodotin in Arm A
Timepoint [15] 0 0
Up to 84 months
Secondary outcome [16] 0 0
Plasma concentrations of total monoclonal antibody (mAb) at indicated time points - Plasma concentrations of total mAb in Arm A
Timepoint [16] 0 0
Up to 84 months
Secondary outcome [17] 0 0
Plasma concentrations of monomethyl auristatin-F with a cysteine linker (cys-mcMMAF) at indicated time points - Plasma concentrations of cys-mcMMAF in Arm A
Timepoint [17] 0 0
Up to 84 months
Secondary outcome [18] 0 0
Maximum observed concentration (Cmax) for pomalidomide - Pharmacokinetic analysis of pomalidomide.
Timepoint [18] 0 0
Up to 24 hours
Secondary outcome [19] 0 0
Time of Cmax (Tmax) for pomalidomide - Pharmacokinetic analysis of pomalidomide.
Timepoint [19] 0 0
Up to 24 hours
Secondary outcome [20] 0 0
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUC[0-t]) for pomalidomide - Pharmacokinetic analysis of pomalidomide.
Timepoint [20] 0 0
Up to 24 hours
Secondary outcome [21] 0 0
Number of participants with positive anti-drug antibodies (ADAs) against belantamab mafodotin - Plasma concentrations of belantamab mafodotin ADAs in Arm A.
Timepoint [21] 0 0
Up to 84 months
Secondary outcome [22] 0 0
Titers of ADAs against belantamab mafodotin - Titers of ADAs in Arm A.
Timepoint [22] 0 0
Up to 84 months
Secondary outcome [23] 0 0
Change from Baseline in symptoms as measured by patient-reported outcome version of the common terminology criteria for adverse events (PRO-CTCAE) - PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trials using a PRO-CTCAE score.
Timepoint [23] 0 0
Baseline and up to 84 months
Secondary outcome [24] 0 0
Change from Baseline in impacts as measured by PRO-CTCAE - PRO-CTCAE questionnaire assesses side effect symptoms in cancer clinical trial. Impacts of the side effects will be assessed using PRO-CTCAE score.
Timepoint [24] 0 0
Baseline and up to 84 months
Secondary outcome [25] 0 0
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) - 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.
Timepoint [25] 0 0
Baseline and up to 84 months
Secondary outcome [26] 0 0
Change from Baseline in HRQoL as measured by EORTC item library 52 (IL52) - 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.
Timepoint [26] 0 0
Baseline and up to 84 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Port Macquarie
Recruitment hospital [2] 0 0
GSK Investigational Site - Wollongong
Recruitment hospital [3] 0 0
GSK Investigational Site - South Brisbane
Recruitment hospital [4] 0 0
GSK Investigational Site - Fitzroy
Recruitment hospital [5] 0 0
GSK Investigational Site - Heidelberg
Recruitment hospital [6] 0 0
GSK Investigational Site - Malvern
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3144 - Malvern
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Hradec Kralove
Country [8] 0 0
France
State/province [8] 0 0
Dijon cedex
Country [9] 0 0
France
State/province [9] 0 0
Marseille Cedex 9
Country [10] 0 0
France
State/province [10] 0 0
Périgueux cedex
Country [11] 0 0
France
State/province [11] 0 0
Toulouse cedex 9
Country [12] 0 0
France
State/province [12] 0 0
Vandoeuvre-Les-Nancy
Country [13] 0 0
Greece
State/province [13] 0 0
Athens
Country [14] 0 0
Greece
State/province [14] 0 0
Larisa
Country [15] 0 0
Greece
State/province [15] 0 0
Rio/Patras
Country [16] 0 0
Greece
State/province [16] 0 0
Thessaloniki
Country [17] 0 0
Italy
State/province [17] 0 0
Emilia-Romagna
Country [18] 0 0
Italy
State/province [18] 0 0
Puglia
Country [19] 0 0
Italy
State/province [19] 0 0
Milano
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Gyeonggi-do
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Hwasun-gun, Jeollanam-do
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Incheon
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seoul
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Navarra
Country [26] 0 0
Spain
State/province [26] 0 0
Badalona
Country [27] 0 0
Spain
State/province [27] 0 0
Barcelona
Country [28] 0 0
Spain
State/province [28] 0 0
Pamplona
Country [29] 0 0
Spain
State/province [29] 0 0
Salamanca
Country [30] 0 0
Spain
State/province [30] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/show/NCT04484623
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04484623