Trial Title:
Study of Belantamab Mafodotin With Carfilzomib, Pomalidomide, and Dexamethasone in Relapsed Multiple Myeloma
NCT ID:
NCT05789303
Condition:
Multiple Myeloma
Relapse Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Pomalidomide
Conditions: Keywords:
multiple myeloma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Belantamab mafodotin
Description:
Cycles 1, 3, 5, 7, etc. (odd numbered cycles): 1.9 mg/kg IV on Day 1 (28-day cycles)
Arm group label:
Cohort 1: No Prior CAR T-Cell Therapy
Arm group label:
Cohort 2: Prior CAR T-Cell Therapy
Other name:
Blenrep
Intervention type:
Drug
Intervention name:
Carfilzomib
Description:
Cycle 1: 20 mg/m2 on Day 1, then 56 mg/m2 on Days 8/15
Cycles 2-8: 56 mg/m2 on Days 1/8/15
Cycles 9+: 56 mg/m2 on Days 1/15
Arm group label:
Cohort 1: No Prior CAR T-Cell Therapy
Arm group label:
Cohort 2: Prior CAR T-Cell Therapy
Other name:
Kyprolis
Intervention type:
Drug
Intervention name:
Pomalidomide
Description:
3 mg Day 1-21 of 28-day Cycle
Arm group label:
Cohort 1: No Prior CAR T-Cell Therapy
Arm group label:
Cohort 2: Prior CAR T-Cell Therapy
Other name:
Pomalyst
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Cycles 1-4: 40 mg Days 1/8/15/22
Cycles 5+: 20 mg Days 1/8/15/22
Arm group label:
Cohort 1: No Prior CAR T-Cell Therapy
Arm group label:
Cohort 2: Prior CAR T-Cell Therapy
Summary:
Doctors leading this study hope to learn if the combination of belantamab mafodotin,
carfilzomib, pomalidomide, and dexamethasone is effective and safe when given to people
who have multiple myeloma that has gotten worse and is not responding to standard drugs
that are used for treating multiple myeloma, including chimeric antigen receptor T-cell
therapy.
Participation in this research will last about 6 -24 months, but it may be less or more
depending on your response to treatment.
Detailed description:
Doctors leading this study hope to learn if the combination of belantamab mafodotin,
carfilzomib, pomalidomide, and dexamethasone is effective and safe when given to people
who have multiple myeloma that has gotten worse and is not responding to standard drugs
that are used for treating multiple myeloma, including chimeric antigen receptor T-cell
therapy.
Participation in this research will last about 6 -24 months, but it may be less or more
depending on your response to treatment.
The purpose of this research is to gather information on the safety and effectiveness of
belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone for patients with a
history of two or more prior lines of myeloma therapy. This combination is not
FDA-approved, although carfilzomib and pomalidomide, are separately FDA-approved agents
in combination with dexamethasone.
Criteria for eligibility:
Criteria:
1. Subject must be ≥ 18 years of age.
2. Life expectancy of more than three months.
3. Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status of
≤ 2
4. Subject must have adequate organ function, defined by clinically confirmed lab
values set by the study team.
5. Female Subjects: contraceptive use should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies.
6. Male Subjects: contraceptive should be used consistently with local regulations
regarding the methods of contraception for those Subjects in clinical studies. Male
Subjects are eligible to participate if they agree to the following during the
intervention period and for six months after the last dose of study treatment 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 a male condom, even if they have undergone a successful
vasectomy, and female partner to use an additional highly effective contraceptive
method with a failure rate of <1% per year as when having sexual intercourse with a
woman of childbearing potential (including pregnant females).
7. 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 enrollment except for alopecia and Grade 2 peripheral neuropathy.
8. Subject must be able to understand the study procedures and agree to participate in
the study by providing written informed consent.
9. Subject must be willing to comply with the requirements consistent with the
belantamab mafodotin and pomalidomide Risk Evaluation and Mitigation Strategy (REMS)
programs.
DISEASE-RELATED:
10. Subjects with relapsed or refractory multiple myeloma requiring systemic therapy,
who have progressed after 2+ prior lines of anti-myeloma treatments. A line of
therapy consists of ≥1 complete cycle of a single agent, a regimen consisting of a
combination of several drugs, or a planned sequential therapy of various regimens.
11. Subjects may be exposed to lenalidomide, bortezomib, daratumumab, elotuzumab,
pomalidomide and/or carfilzomib.
12. If NO prior CAR T-cell therapy: Subjects who have been deemed refractory to EITHER
carfilzomib or pomalidomide are permitted but subjects cannot be refractory to both
carfilzomib and pomalidomide. Refractoriness is defined here as disease which was
non-responsive or progressive while on therapy or within 60 days of the last
treatment in patients who had achieved a minimal response or better on prior
therapy.
13. If prior CAR T-cell therapy: Subjects whose most recent line of therapy was
anti-B-cell maturation antigen (BCMA) targeted CAR T-cell therapy are permitted to
enroll, regardless of carfilzomib/pomalidomide refractory status, if they meet
criteria for progression.
14. Measurable disease, as indicated by one or more of the following:
1. Serum M-protein of 0.5 g/dL of greater. If serum protein electrophoresis is
felt to be unreliable for routine M-protein measurement (i.e. M-spike in the
beta region), then quantitative immunoglobulin levels are acceptable
(Immunoglobulin-A, Immunoglobulin-M, or Immunoglobulin-D > 600 mg/dL or
Immunoglobulin-G> 1100 mg/dL).
2. Urine M-protein ≥ 200 mg/24 hours.
3. Involved serum free light chains ≥ 10 mg/dL provided that free light chain
ratio is abnormal.
15. Subjects must receive insurance approval for pomalidomide and dexamethasone.
Exclusion criteria
Disease Related
1. Waldenström's macroglobulinemia, systemic amyloidosis, POEMS syndrome, or plasma
cell leukemia at the time of screening.
2. Radiotherapy to multiple sites within 3 weeks before start of protocol treatment
(localized radiotherapy to a single site 1 week before start is permissible).
3. Subject must not have used an investigational drug or approved systemic anti-myeloma
therapy (including systemic steroids) within 14 days preceding the first dose of
study drug.
4. Prior refractory status to belantamab mafodotin. Concurrent Conditions
5. Current corneal epithelial disease except mild changes in corneal epithelium and
mild punctate keratopathy.
6. Subject must not have current unstable liver or biliary disease defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or
gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic
chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or
hepatobiliary involvement of malignancy is acceptable if otherwise meets entry
criteria.
7. Subject must not have presence of active renal condition (infection, requirement for
dialysis or any other condition that could affect Subject's safety). Subjects with
isolated proteinuria resulting from multiple myeloma (MM) are eligible, provided
they fulfil the inclusion criteria.
8. Subject must not use contact lenses while participating in this study unless
instructed by an ophthalmologist.
9. Subject must not be simultaneously enrolled in any interventional clinical trial.
10. Subject must not have had major surgery ≤ 2 weeks prior to initiating study
treatment.
11. Subject must not have any evidence of active mucosal or internal bleeding.
12. Significant neuropathy (Grades 3-4, or Grade 2 with pain) at the time of the first
dose and/or within 14 days before enrollment.
13. Subject must not have evidence of cardiovascular risk including any of the
following:
1. Evidence of current clinically significant uncontrolled arrhythmias, including
clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or
3rd degree atrioventricular (AV) block. Controlled atrial fibrillation is not
an exclusion.
2. History of myocardial infarction, acute coronary syndromes, coronary
angioplasty, or stenting or bypass grafting within three (3) months of
screening.
3. Class III or IV heart failure as defined by the New York Heart Association
functional classification system
4. Uncontrolled hypertension.
14. Subject must not have known immediate or delayed hypersensitivity reaction or
idiosyncratic reactions to belantamab mafodotin or drugs chemically related to
belantamab mafodotin, or any of the components of the study treatment.
15. Subject must not have an active infection requiring treatment.
16. Subject with HIV infection will be excluded unless certain T-cell count, viral load
and clinical qualifications are met as confirmed by the study doctor
Note: consideration must be given to anti-retroviral and prophylactic antimicrobials
that may have a drug:drug interaction and/or overlapping toxicities with belantamab
mafodotin or other combination products as relevant.
17. Patients with Hepatitis B will be excluded unless certain clinical criteria are met
as confirmed by the study doctor.
18. Subject must not have positive hepatitis C antibody test result or positive
hepatitis C Ribonucleic acid test result at screening or within 3 months prior to
first dose of study treatment unless the subject can meet the following criteria:
(1) Hepatitis C Ribonucleic acid test is negative (2) Receives successful anti-viral
treatment (typically 8 weeks) followed by a negative nucleocapsid ribonucleic acid test
after a washout period of at least 4 weeks.
Note: Subjects with positive Hepatitis C antibody due to prior resolved disease can be
enrolled, only if a confirmatory negative Hepatitis C test is obtained.
19. Subject must not have invasive malignancies other than disease under study, unless
the second malignancy has been medically stable for at least 2 years and, in the
opinion of the principal investigators, will not affect the evaluation of the
effects of clinical trial treatments on the currently targeted malignancy. Subjects
with curatively treated non-melanoma skin cancer may be enrolled without a 2-year
restriction.
20. Subject must not have any serious and/or unstable pre-existing medical, psychiatric
disorder, or other conditions (including lab abnormalities) that could interfere
with Subject's safety, obtaining informed consent or compliance to the study
procedures.
21. Subjects must not be pregnant or lactating.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Chicago Medicine Comprehensive Cancer Center
Address:
City:
Chicago
Zip:
60637
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Intake
Phone:
855-702-8222
Email:
cancerclinicaltrials@bsd.uchicago.edu
Start date:
May 30, 2023
Completion date:
July 1, 2028
Lead sponsor:
Agency:
University of Chicago
Agency class:
Other
Collaborator:
Agency:
GlaxoSmithKline
Agency class:
Industry
Collaborator:
Agency:
Amgen
Agency class:
Industry
Source:
University of Chicago
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05789303
