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Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT04162210

Description:

This open-label, randomized study for evaluating the efficacy and safety of single agent belantamab mafodotin when compared to pom/dex in participants with RRMM. Participants will be randomized in a 2:1 ratio to receive either single agent belantamab mafodotin or pom/dex. Belantamab mafodotin will be administered intravenously at 2.5 milligram (mg)/kilogram (kg) on Day 1 (D1) of an every 3 weeks (Q3W) schedule. Pomalidomide will be administered orally at the approved starting dose of 4 mg daily on Days 1 to 21 of each 28-day cycle, with dexamethasone administered orally at a dose of 40 mg once weekly (Days 1, 8, 15, and 22). Participants in both arms will be treated until disease progression, death, unacceptable toxicity, withdrawal of consent, and lost to follow-up or end of study, whichever comes first. Approximately up to 380 participants will be randomized (320 + 60 to fulfill regional country requirements).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Single Agent Belantamab Mafodotin Versus Pomalidomide Plus Low-dose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)
  • Official Title: A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Single Agent Belantamab Mafodotin Compared to Pomalidomide Plus Lowdose Dexamethasone (Pom/Dex) in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 3)

Clinical Trial IDs

  • ORG STUDY ID: 207495
  • NCT ID: NCT04162210

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinParticipants receiving Belantamab mafodotin
Pom/dex (Pomalidomide plus low dose Dexamethasone)Participants receiving pom/dex

Purpose

This open-label, randomized study for evaluating the efficacy and safety of single agent belantamab mafodotin when compared to pom/dex in participants with RRMM. Participants will be randomized in a 2:1 ratio to receive either single agent belantamab mafodotin or pom/dex. Belantamab mafodotin will be administered intravenously at 2.5 milligram (mg)/kilogram (kg) on Day 1 (D1) of an every 3 weeks (Q3W) schedule. Pomalidomide will be administered orally at the approved starting dose of 4 mg daily on Days 1 to 21 of each 28-day cycle, with dexamethasone administered orally at a dose of 40 mg once weekly (Days 1, 8, 15, and 22). Participants in both arms will be treated until disease progression, death, unacceptable toxicity, withdrawal of consent, and lost to follow-up or end of study, whichever comes first. Approximately up to 380 participants will be randomized (320 + 60 to fulfill regional country requirements).

Trial Arms

NameTypeDescriptionInterventions
Participants receiving Belantamab mafodotinExperimentalParticipants will receive belantamab mafodotin single agent dose of 2.5 mg/kg on Day 1 of Q3W
  • Belantamab mafodotin
Participants receiving pom/dexActive ComparatorParticipants will receive pomalidomide orally starting dose of 4 mg daily on Days 1 to 21 of each 28-cycle, with dexamethasone at an oral dose of 40 mg once weekly or a lower dose of 20 mg once weekly on Days 1, 8, 15 and 22.
  • Pom/dex (Pomalidomide plus low dose Dexamethasone)

Eligibility Criteria

        Inclusion Criteria:

          -  Capable of giving signed informed consent.

          -  Participants must be 18 or older, at the time of signing the informed consent. In
             Republic of Korea, participants must be over 19 years of age inclusive, at the time of
             signing informed consent.

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

          -  Histologically or cytologically confirmed diagnosis of Multiple myeloma (MM) as
             defined according to IMWG, and : Has undergone autologous stem cell transplant (SCT),
             or is considered transplant ineligible; Has received at least 2 prior lines of
             anti-myeloma treatments, including at least 2 consecutive cycles of both lenalidomide
             and a proteasome inhibitor (given separately or in combination), and must have
             documented disease progression on, or within 60 days of, completion of the last
             treatment as defined by IMWG.

          -  Has measurable disease with at least one of the following: Serum M-protein >=0.5 gram
             per deciliter (g/dL) (>=5 gram per Liter); Urine M-protein >=200 mg/24 hours; Serum
             free light chain (FLC) assay: Involved FLC level >=10 milligram per deciliter (mg/dL)
             (>=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).

          -  Participants with a history of autologous SCT are eligible for study participation
             provided the following eligibility criteria are met: Transplant was >100 days prior to
             initiating study treatment; No active infection(s).

          -  Adequate organ system functions as defined: Absolute neutrophil count (ANC)
             >=1.0*10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 50x10^9/L; Total bilirubin <=1.5*
             Upper limit of normal (ULN) (isolated bilirubin >1.5*ULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35 percent); ALT <=2.5*ULN; Estimated glomerular
             filtration rate (eGFR) >=30 milliliter per minute per 1.73 square meter (mL/min/1.73
             m^2); Spot urine (albumin/creatinine ratios) <=500 milligram per gram (mg/g) (56
             milligram per millimoles [mg/mmol]); Left ventricular ejection fraction (LVEF)
             (echocardiogram) Clinically asymptomatic participants with ECHO confirmed LVEF>=25
             percent

          -  Contraceptive use by men or women should be consistent with local regulations
             regarding the methods of contraception for those participating in clinical studies.
             Male participants are eligible to participate if they agree to the following during
             the intervention period and until 5 months after the last dose of study intervention
             to allow for clearance of any altered sperm: Refrain from donating sperm PLUS, either:
             Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
             (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must
             agree to use contraception/barrier as detailed below depending on whether they are
             randomised to Arm 1 (belantamab mafodotin) or Arm 2 (pom/dex), even if they have
             undergone a successful vasectomy: Agree to use a male condom throughout study
             treatment including the 5 month* follow-up period even if they have undergone a
             successful vasectomy and a female partner to use an additional highly effective
             contraceptive method with a failure rate of <1 percent per year when having sexual
             intercourse with a pregnant woman or a woman of childbearing potential who is not
             currently pregnant. * Four weeks for male participants on Treatment Arm 2 (pom/dex).

          -  A female participant is eligible to participate if she is not pregnant or
             breastfeeding, and at least one of the following conditions applies: Is not a woman of
             childbearing potential (WOCBP) OR Is a WOCBP and agrees to abide by the following: Arm
             1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a
             failure rate of <1 percent per year) which includes abstinence, preferably with low
             user dependency during the intervention period and for 8 months after the last dose of
             study treatment. Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue
             with risk for embryofetal toxicity and prescribed under a pregnancy
             prevention/controlled distribution program, WOCBP participants will be eligible if
             they commit either to abstain continuously from heterosexual sexual intercourse or to
             use two methods of reliable birth control (one method that is highly effective),
             beginning 4 weeks prior to initiating treatment with pomalidomide, during therapy,
             during dose interruptions and continuing for at least 4 weeks following
             discontinuation of pomalidomide treatment. Two negative pregnancy tests must be
             obtained prior to initiating therapy. The first test should be performed within 10-14
             days and the second test within 24 hours prior to prescribing pomalidomide therapy.
             And agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during
             this period. The investigator should confirm the effectiveness of the contraceptive
             method(s) ahead of the first dose of study intervention.

          -  All prior treatment-related toxicities (defined by National Cancer Institute- Common
             Toxicity Criteria for Adverse Events [NCI-CTCAE], version 5.0, 2017) must be <=Grade 1
             at the time of enrollment, except for alopecia and Grade 2 peripheral neuropathy.

          -  In France, a participant will be eligible for inclusion in this study only if either
             affiliated to or a beneficiary of a social security category.

        Exclusion Criteria:

          -  Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly,
             endocrinopathy, myeloma protein, and skin changes); active plasma cell leukemia at the
             time of screening.

          -  Systemic anti-myeloma therapy or use of an investigational drug within <14 days or 5
             half-lives, whichever is shorter, before the first dose of study intervention.

          -  Prior treatment with an anti-MM monoclonal antibody within 30 days prior to receiving
             the first dose of study intervention.

          -  Prior B cell maturation antigen (BCMA)-targeted therapy or prior pomalidomide
             treatment.

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

          -  Prior allogeneic stem cell transplant.

          -  Any major surgery within the last 4 weeks.

          -  Presence of active renal condition (infection, requirement for dialysis or any other
             condition that could affect participant's safety). Participants with isolated
             proteinuria resulting from MM are eligible, provided they fulfil criteria.

          -  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.

          -  History of (non-infectious) pneumonitis that required steroids, or current
             pneumonitis.

          -  Evidence of active mucosal or internal bleeding.

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

          -  Participants with previous or concurrent malignancies other than multiple myeloma are
             excluded, unless the second malignancy has been considered medically stable for at
             least 2 years. The participant must not be receiving active therapy, other than
             hormonal therapy for this disease.

          -  Evidence of cardiovascular risk including any of the following: QT interval corrected
             for heart rate by Fridericia's formula (QTcF) >= 480 millisecond (msec); Evidence of
             current clinically significant uncontrolled arrhythmias including clinically
             significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz Type
             II) or 3rd degree atrioventricular block; History of myocardial infarction, acute
             coronary syndromes (including unstable angina), coronary angioplasty, or stenting or
             bypass grafting within 3 months of Screening; Class III or IV heart failure as defined
             by the New York Heart Association (NYHA) functional classification system;
             Uncontrolled hypertension.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to belantamab mafodotin, pomalidomide, dexamethasone or any of the
             components of the study intervention.

          -  Pregnant or lactating female.

          -  Active infection requiring treatment.

          -  Known human immunodeficiency virus (HIV).

          -  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 intervention.

          -  Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid
             (RNA) test result at screening or within 3 months prior to first dose of study
             intervention.

          -  Participants unable to tolerate thromboembolic prophylaxis.
      
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 20 months
Safety Issue:
Description:PFS, defined as the time from the date of randomization until the earliest date of documented disease progression (according to International Myeloma Working Group [IMWG] Response Criteria) or death due to any cause

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 55 months
Safety Issue:
Description:OS, defined as the time from randomization until death due to any cause
Measure:Overall response rate (ORR)
Time Frame:Up to 55 months
Safety Issue:
Description:ORR, defined as the percentage of participants with a confirmed partial response (PR) or better per IMWG
Measure:Clinical benefit rate (CBR)
Time Frame:Up to 55 months
Safety Issue:
Description:CBR defined as the percentage of participants with a confirmed minimal response (MR) or better per IMWG
Measure:Duration of response (DoR)
Time Frame:Up to 55 months
Safety Issue:
Description:DoR, defined as the time from first documented evidence of PR or better until progressive disease (PD) per IMWG or death due to PD among participants who achieve confirmed PR or better
Measure:Time to response (TTR)
Time Frame:Up to 55 months
Safety Issue:
Description:TTR, defined as the time between the date of randomization and the first documented evidence of response (PR or better) among participants who achieve confirmed PR or better.
Measure:Time to progression (TTP)
Time Frame:Up to 55 months
Safety Issue:
Description:TTP, defined as the time from the date of randomization until the earliest date of documented PD (per IMWG Response Criteria) or death due to PD
Measure:Number of participants with adverse events (AEs)
Time Frame:Up to 55 months
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before.
Measure:Change from Baseline in hematology parameters: absolute white blood cell count (WBC), basophils,eosinophils, lymphocytes, monocytes, platelet count, and neutrophils (Giga cells per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of hematology parameters
Measure:Change from Baseline in hematology parameters: Red Blood Cell (RBC) count and reticulocyte count (Trillion cells per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of hematology parameters
Measure:Change from Baseline in hematology parameters: Mean Corpuscular Hemoglobin concentration (MCHC) and hemoglobin (Grams per Liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of hematology parameters
Measure:Change from Baseline in hematology parameters: Hematocrit (Proportion of red blood cells in blood)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of hematology parameters
Measure:Change from Baseline in hematology parameters: Mean Corpuscular Volume (MCV) [Femtoliter]
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of hematology parameters
Measure:Change from Baseline in hematology parameters: Mean Corpuscular Hemoglobin (MCH) [Picograms]
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of hematology parameters
Measure:Change from Baseline in clinical chemistry parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine kinase (CK), Gamma Glutamyl Transferase (GGT), and lactate dehydrogenase (LDH)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of clinical chemistry parameters like ALT, AST, ALP, CK, GGT, and LDH [International units per Liter]
Measure:Change from Baseline in clinical chemistry parameters: Calcium, chloride, glucose, potassium, sodium, magnesium, blood urea nitrogen (BUN), and phosphorous (Millimoles per Liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of clinical chemistry parameters
Measure:Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin, uric acid (Micromoles per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of clinical chemistry parameters
Measure:Change from Baseline in clinical chemistry parameters: Albumin and total protein (Grams per Liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time-points for the analysis of clinical chemistry parameters
Measure:Change from Baseline in Urinalysis Parameter: Specific Gravity (Ratio)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity.
Measure:Change from Baseline in Urinalysis Parameters- Urine potential of hydrogen (pH) (Points on a scale)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of Urinary pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Measure:Change from Baseline in urinalysis parameter: Glucose (Millimole per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of urinary glucose.
Measure:Change from Baseline in urinalysis parameter: Protein (Grams per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of urinary protein.
Measure:Change from Baseline in urinalysis parameter: Ketones (Millimoles per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of urinary ketones.
Measure:Change from Baseline in urinalysis parameter: blood (10^9 cells per liter)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of urinary blood.
Measure:Change from Baseline in urinalysis parameter: creatinine/albumin ratio (ratio)
Time Frame:Baseline and up to 55 months
Safety Issue:
Description:Urine samples will be collected at indicated time points for the assessment of urinary creatinine/albumin ratio.
Measure:Number of participants with abnormal ocular findings
Time Frame:Up to 55 months
Safety Issue:
Description:Participants will be assessed for any abnormal ocular findings
Measure:Plasma concentrations of belantamab mafodotin
Time Frame:Up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time points for the analysis
Measure:Plasma concentrations of total monoclonal antibody (mAb)
Time Frame:Up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time points for the analysis
Measure:Plasma concentrations of cys-mc Microtubular inhibitor monomethyl auristatin-F (MMAF)
Time Frame:Up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time points for the analysis
Measure:Number of participants with Anti-drug antibody (ADAs) against belantamab mafodotin
Time Frame:Up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time points for the analysis
Measure:Titer of ADAs against belantamab mafodotin
Time Frame:Up to 55 months
Safety Issue:
Description:Blood samples will be collected at indicated time points for the analysis
Measure:Number of participants with symptomatic adverse effects measured by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Time Frame:Up to 55 months
Safety Issue:
Description:PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. The PRO-CTCAE includes an item library of 124 items representing 78 symptomatic toxicities drawn from the CTCAE.
Measure:Number of participants with symptomatic adverse effects measured by Ocular Surface Disease Index (OSDI)
Time Frame:Up to 55 months
Safety Issue:
Description:OSDI is a 12-item questionnaire designed to assesses both the frequency of dry eye symptoms and their impact on vision-related functioning
Measure:European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQC30) score
Time Frame:Up to 55 months
Safety Issue:
Description:The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/quality of life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each scale and single-item measure are averaged and transformed linearly to a score ranging from 0-100.
Measure:European Organization for Research and Treatment of Cancer IL52 (EORTC IL52) score
Time Frame:Up to 55 months
Safety Issue:
Description:The EORTC Quality of Life Questionnaire 20-item Multiple Myeloma module (QLQMY20) is a supplement to the QLQ-C30 instrument used in participants with multiple myeloma. Disease Symptoms domain of the QLQ-MY20 will be used for bone aches or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity. QLQ-C30, QLQ-MY20 domain scores are averaged and transformed linearly to a score ranging from 0-100. A high score for Disease Symptoms represents a high level of symptomatology or problems
Measure:Rate of Minimal Residual Disease (MRD)
Time Frame:Up to 55 months
Safety Issue:
Description:MRD negativity rate, defined as; the percentage of participants who are MRD negative by Next generation sequencing (NGS) method

Details

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

Trial Keywords

  • Belantamab mafodotin
  • Pomalidomide
  • Dexamethasone
  • Relapsed/Refractory Multiple Myeloma

Last Updated

April 7, 2020