Trial Title:
Alternate Doses and Dosing Schedules of Belantamab Mafodotin for Treatment of Triple-Class Refractory Multiple Myeloma
NCT ID:
NCT05847569
Condition:
Recurrent Multiple Myeloma
Refractory Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Belantamab Mafodotin
Description:
Given IV
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
Belantamab Mafodotin-blmf
Other name:
Blenrep
Other name:
GSK2857916
Other name:
J6M0-mcMMAF
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspirate
Description:
Undergo bone marrow aspirate
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
BONE MARROW, LIQUID
Other name:
Human Bone Marrow Aspirate
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo biopsy
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Other name:
Computerized Tomography (CT) scan
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI scan
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
Magnetic Resonance Imaging (MRI)
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT scan
Arm group label:
Group I (low dose belantamab mafodotin)
Arm group label:
Group II (low dose and high dose belantamab mafodotin)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Summary:
This phase II trial tests alternate doses and dosing schedules of belantamab mafodotin in
treating patients with triple-class multiple myeloma that has come back (after a period
of improvement) (recurrent) and/or does not respond to treatment (or that has not
responded to previous treatment) (refractory). Belantamab mafodotin is a monoclonal
antibody, belantamab, linked to a chemotherapy drug, mafodotin. Belantamab is a form of
targeted therapy because it attaches to specific molecules (receptors) on the surface of
cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. This trial
may help researchers determine if alternate doses and dosing schedules work better in
preventing certain side effects, such as eye toxicity, and treating patients with
recurrent or refractory multiple myeloma.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess the grade 3/4 keratopathy-free rate at the time of dose #4 of an alternative
dose/dosing schedule of belantamab mafodotin in patients with relapsed or refractory
multiple myeloma (RRMM).
SECONDARY OBJECTIVES:
I. To assess the overall response rate (ORR; partial response or better) of an
alternative dose/dosing schedule of belantamab mafodotin in patients with RRMM.
II. To assess the safety of an alternative dose/dosing schedule of belantamab mafodotin
in patients with RRMM.
III. To assess the time to progression (TTP) of an alternative dose/dosing schedule of
belantamab mafodotin in patients with RRMM.
IV. To assess the progression free survival (PFS) with an alternative dose/dosing
schedule of belantamab mafodotin in patients with RRMM.
V. To assess the overall survival (OS) with an alternative dose/dosing schedule of
belantamab mafodotin in patients with RRMM.
VI. To assess the minimal residual disease (MRD) negativity rate in patients who have
achieved a complete response (CR) with an alternative dose/dosing schedule of belantamab
mafodotin.
CORRELATIVE AND PHARMACODYNAMIC RESEARCH OBJECTIVES:
I. To assess the association of pre-treatment serum BCMA levels as well as serum BCMA
levels throughout treatment with ORR and PFS to an alternative treatment schedule of
belantamab mafodotin.
II. To assess the pharmacokinetics of this alternative dose/dosing schedule of belantamab
mafodotin.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive low dose belantamab mafodotin intravenously (IV) on day 1 of
each cycle. Cycles repeat every 6 weeks in the absence of disease progression or
unacceptable toxicity. All patients undergo a computed tomography (CT) scan, a magnetic
resonance image (MRI) scan, or a positron emission tomography (PET)/CT scan during
screening and patients with plasmacytoma (a multiple myeloma [MM] tumor in bone or soft
tissue) also undergo imaging scans on study. Patients undergo bone marrow aspirate and
biopsy during screening and on study as well as collection of blood samples throughout
the trial.
GROUP II: Patients receive belantamab mafodotin IV on day 1. Cycle repeasts at 3 weeks
for the next cycle and then every 6 weeks for subsequent cycles in the absence of disease
progression or unacceptable toxicity. All patients undergo a CT scan, a MRI scan, or a
PET/CT scan during screening and patients with plasmacytoma (a MM tumor in bone or soft
tissue) also undergo imaging scans on study. Patients undergo bone marrow aspirate and
biopsy during screening and on study as well as collection of blood samples throughout
the trial.
After completion of trial treatment, patients are followed up every 12 weeks for up to 5
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
- Histologically or cytologically confirmed diagnosis of multiple myeloma (MM), as
defined in International Myeloma Working Group (IMWG) criteria, and:
- If patients have undergone stem cell transplantation (SCT), day 0 of SCT must
be > 100 days prior to registration to be eligible for the study
- Has had disease progression after >= 3 prior lines of anti-myeloma
treatments including one proteasome inhibitor (eg. bortezomib, carfilzomib or
ixazomib), one immunomodulatory agent (eg.thalidomide, lenalidomide or
pomalidomide) and one anti-CD38 monoclonal antibody (eg.daratumumab or
isatuximab)
- Prior non-belantamab mafodotin anti-BCMA agent exposure is allowed; patients
with prior treatment with an anti-BCMA chimeric antigen receptor (CAR)-T or
bispecific antibody will be allowed to participate in the study
- Has measurable disease with at least one of the following:
- Serum M-protein >= 0.5 g/dL (>= 5 g/L)
- Urine M-protein >= 200 mg/24 h
- Serum free light chain (FLC) assay: Involved FLC level >= 10 mg/dL (>=
100 mg/L) and an abnormal serum free light chain ratio (< 0.26 or > 1.65)
- Note: Patients with non-secretory disease will be allowed to participate
- Absolute neutrophil count >= 0.75 x 10^9/L (=< 28 days prior to registration)
- Without growth factor support, blood transfusion, or platelet stimulating
agents for the past 14 days, excluding erythropoietin
- Hemoglobin >= 7.0 g/dL (=< 28 days prior to registration)
- Without growth factor support, blood transfusion, or platelet stimulating
agents for the past 14 days, excluding erythropoietin
- Platelets >= 50 x 10^9/L (=< 28 days prior to registration)
- Without growth factor support, blood transfusion, or platelet stimulating
agents for the past 14 days, excluding erythropoietin
- Total bilirubin =< 2.0 x upper limit of normal (ULN) (=< 28 days prior to
registration); (Isolated bilirubin >= 2.0 x ULN is acceptable if bilirubin is
fractionated and direct bilirubin is < 35%)
- Alanine aminotransferase =< 2.5 x ULN (=< 28 days prior to registration)
- Aspartate transaminase =< 2.5 x ULN (=< 28 days prior to registration)
- Estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m^2 (=< 28 days
prior to registration)
- As calculated by Modification of Diet in Renal Disease (MDRD) formula
- Spot urine (albumin/creatinine ratios [spot urine]) =< 500 mg/g (56 mg/mmol) OR
urine dipstick negative/trace (if >1+ only eligible if confirmed =< 500 mg/g
[56 mg/mmol] by albumin/creatinine ratio [spot urine from first void]) (=< 28
days prior to registration)
- Negative pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only. Both females and males must agree to follow the
instructions
- NOTE: If the urine test is positive or cannot be confirmed as negative, a serum
pregnancy test will be required
- Provide written informed consent which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in the study protocol
- Willingness to provide mandatory blood specimens for correlative research
- Willing to return to enrolling institution for follow-up (during the Active
Monitoring Phase of the study)
Exclusion Criteria:
- Active plasma cell leukemia at the time of screening. Symptomatic amyloidosis,
active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal
plasmaproliferative disorder, myeloma protein, and skin changes), Waldenstrom
Macroglobulinemia
- The only exception is emergency use of a short course of systemic corticosteroids
(equivalent to, or less than: dexamethasone 40 mg/day for a maximum of 4 days)
before treatment
- Prior belantamab mafodotin therapy. However, patients with prior exposure to another
non-belantamab mafodotin anti-BCMA agent such as an anti-BCMA CAR-T or anti-BCMA
bispecific antibody will be allowed to participate in the study
- Systemic active infection requiring treatment
- Any unresolved toxicity >= grade 2 from previous treatment except for alopecia,
or peripheral neuropathy up to grade 2
- Any major surgery =< 4 weeks prior to registration
- Any serious and/or unstable pre-existing medical, psychiatric disorder or other
conditions (including lab abnormalities except renal impairment) that could
interfere with participant's safety, obtaining informed consent or compliance to the
study procedures
- Evidence of active mucosal or internal bleeding
- Current unstable liver or biliary disease per investigator assessment defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver
disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary
involvement of malignancy is acceptable if participant otherwise meets entry
criteria
- Participants with previous or concurrent malignancies other than multiple myeloma
are excluded, unless the prior malignancy has been considered medically stable for
> 2 years. The participant must not be receiving active therapy, other than
hormonal therapy for this disease. NOTE: Participants with curatively treated
nonmelanoma skin cancer are allowed without a 2-year restriction.
- Evidence of cardiovascular risk, including any of the following:
- Evidence of current clinically significant untreated arrhythmias, including
clinically significant electrocardiogram (ECG) abnormalities including 2nd
degree (Mobitz type II) or 3rd degree atrioventricular (AV) block
- History of myocardial infarction (=< 6 months), acute coronary syndromes
(including unstable angina), coronary angioplasty, or stenting or bypass
grafting within 12 weeks of screening
- Class III or IV heart failure as defined by the New York Heart Association
functional classification system [NYHA, 1994]
- Uncontrolled hypertension
- Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to
drugs chemically related to belantamab mafodotin, or any of the components of the
study treatment
- Known human immunodeficiency virus (HIV) infection, unless the participant can meet
all of the following criteria:
- Established anti-retroviral therapy (ART) for at >=4 weeks and HIV viral
load < 400 copies/mL
- CD4+ T-cell (CD4+) counts >= 350 cells/uL
- No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic
infections < 12 months prior
- Note: consideration must be given to ART and prophylactic antimicrobials that
may have a drug-drug interaction and/or overlapping toxicities with belantamab
mafodotin or other combination products as relevant
- Patients with hepatitis B will be excluded unless the following criteria can be met:
- If patient's serology shows hepatitis B virus core antibody (HbcAb)+ and
hepatitis B surface antigen (HbsAg)-, they must have undetectable hepatitis B
virus (HBV) deoxyribonucleic acid (DNA) at screening. Patients will be
monitored per protocol. Antiviral treatment would be instituted if HBV DNA
becomes detectable
- If patient's serology shows HBsAg+ at screen or within 3 months prior, patients
must have undetectable HBV DNA at screening, must have started highly effective
antiviral treatment at least 4 weeks prior to registration, and must have
baseline imaging per protocol (patients with cirrhosis are excluded). Patients
must remain on antiviral treatment throughout the study. Patients will be
monitored per protocol
- Note: presence of hepatitis (Hep) B surface antibody (HBsAb) indicating
previous vaccination will not exclude a participant.
- Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid
(RNA) test result at screening or =< 12 weeks prior to first dose of study
treatment unless the participant can meet the following criteria:
- RNA test negative
- Successful anti-viral treatment (usually 8 weeks duration) is required,
followed by a negative HCV RNA test after a washout period >= 4 weeks
- Current corneal epithelial disease except for mild punctuate keratopathy
- Participant who received plasmapheresis within =< 7 days prior to registration
- Patients who received prior allogeneic stem cell transplant
- Participant who received a live or live-attenuated vaccine =< 30 days prior to
registration. Ok to receive coronavirus disease (COVID) vaccine at any timepoint
during protocol treatment
- Participant is a woman who is pregnant or lactating
- Participant who plans on wearing contact lenses during treatment with belantamab
mafodotin
Lifestyle Considerations:
Contact lenses are prohibited for participants while they are receiving belantamab
mafodotin treatment. Contact lens use may be restarted after belantamab mafodotin
treatment is discontinued, provided a qualified eye care specialist confirm there are no
other contraindications. Use of bandage contact lenses is allowed for the treatment of
corneal epithelial disease as prescribed by an ophthalmologist/eye care professional.
No other lifestyle restrictions are required for participants in this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Florida
Address:
City:
Jacksonville
Zip:
32224-9980
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Contact backup:
Last name:
Ricardo D. Parrondo, M.D.
Start date:
January 4, 2024
Completion date:
May 29, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05847569
https://www.mayo.edu/research/clinical-trials
