Inclusion Criteria:
Participant must be able to understand the study procedures. 1. Patient is, in the investigator's opinion, willing and able to comply with the
protocol requirements.
2. Patient has given voluntary written informed consent before performance of any
study-related procedure nor part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their future
medical care.
3. Relapse multiple myeloma patients that have received at least 1 and no more than 3
prior lines of therapy. Induction, intensification with high-dose melphalan and stem
cell transplant and maintenance is considered one line of treatment.
4. Patients must be refractory to lenalidomide. Refractoriness is defined as progression
while receiving lenalidomide or in the first 60 days after the last dose of
lenalidomide.
Refractoriness would be defined regardless of the dose of lenalidomide received, and
the schedule or whether it was given alone or in combination.
5. Patients can have received prior treatment with proteasome inhibitors. Patients with
prior bortezomib treatment are eligible regardless of refractory status. Prior
carfilzomib treatment is allowed, provided that the patients achieve at least a
partial response to prior carfilzomib, and that there is a treatment free interval of
at least 6 months.
6. Participant must have a measurable secretory disease defined as either serum
monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24
h. For patients whose disease is only measurable by serum FLC, the involved FLC should
be ≥ 10mg/L (100 mg/dl), with an abnormal serum FLC ratio.
7. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
of ≤ 2. 8. Participant must be ≥ 18 years of age. 9. Participant must have adequate organ function. Laboratory values that define adequate
organ function for inclusion in study are as follow:
HEMATOLOGIC Absolute neutrophil count (ANC) ≥1.5 X 109/L Hemoglobin ≥8.0 g/dL (prior
red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted)
Platelets ≥75 x 109/L for subjects in whom <50% of bone marrow nucleated cells are
plasma cells; otherwise platelet count >50 × 10*9/L (prior platelet transfusion is
permitted up to 7 days before the screening phase) Calcium corrected serum calcium <14
mg/dL (<3.5 mmol/L); or free ionized calcium <6.5 mg/dL (<1.6 mmol/L); HEPATIC Total
bilirubin ≤1.5X ULN (Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%) ALT ≤2.5 X ULN AST ≤2.5 X ULN. RENAL eGFRa ≥40 mL/min/ 1.73 m2 Spot urine (albumin/creatinine ratios) <500 mg/g (56
mg/mmol) OR Negative/trace (if ≥1+ only eligible if confirmed ≥ 500 mg/g (56 mg/mmol)
by albumin/creatinine ratio (spot urine from first void) Urine Dipstick. CARDIAC LVEF (echo) ≥ 40%
10. Female participants: contraceptive use should be consistent with local regulations
regarding the methods of contraception for those participating in clinical studies. 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 using a contraceptive method that is highly effective (with a
failure rate of <1% per year), preferably with low user dependency, during the
intervention period and for at least 4 months after the last dose of study
intervention and agrees not to donate eggs (ova, oocytes) for the purpose of
reproduction during this period.
The investigator should evaluate the
effectiveness of the contraceptive method in relationship to the first dose of
study intervention.
A WOCBP must have a negative highly sensitive serum pregnancy test (as required by
local regulations) within 72 hours before the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and
recent sexual activity to decrease the risk for inclusion of a woman with a nearly
undetected pregnancy.
Nonchildbearing potential is defined as follows (by other than medical reasons):
- - ≥45 years of age and has not had menses for >1 year.
- - Patients who have been amenorrhoeic for >2 years without history of a
hysterectomy and oophorectomy must have a follicle stimulating hormone value in
the postmenopausal range upon screening evaluation.
- - Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
Documented
hysterectomy or oophorectomy must be confirmed with medical records of the actual
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with
medical records of the actual procedure.
11. Male participants: contraceptive use 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 from the
time of first dose of study until 6 months after the last dose of belantamab mafodotin
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:
- 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 when having sexual
intercourse with a WOCBP (including pregnant females).
12. All prior treatment-related toxicities (defined by National Cancer Institute- Common
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 must be ≤ Grade 1 at the
time of enrolment except for alopecia. 13. Participant must be able to understand the study procedures and agree to participate
in the study by providing written informed consent.
Exclusion Criteria:
1. Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of
undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell
leukemia or active POEMS syndrome at the time of screening.
2. Participant has 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. Participants with
curatively treated non-melanoma skin cancer may be enrolled without a 2-year
restriction.
3. Participant has meningeal involvement of multiple myeloma.
4. Pregnant or breastfeeding females.
5. Participant is simultaneously enrolled in other interventional clinical trial.
6. Participant has used a systemic anti-myeloma drug within 14 days or five half-lives,
whichever is shorter, preceding the first dose of study drug.
7. Participant has used an investigational drug within 14 days or five half-lives,
whichever is shorter, preceding the first dose of study drug.
8. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose
of study drug.
9. Participant has received prior treatment with anti-BCMA agents.
10. Received plasmapheresis within 7 days prior to the first dose of study drug.
11. Participant has received prior radiotherapy within 2 weeks of start of study therapy.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system
(CNS) disease.
12. Participant has a 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.
13. Participant has a known immediate or delayed hypersensitivity reaction or idiosyncrasy
to other molecular antibodies.
14. Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
15. Participant has current corneal epithelial disease except mild changes in corneal
epithelium. 16. Participant has peripheral neuropathy or neuropathic pain grade ≥2, as defined by the
National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version
4.0.
17. Participant evidence of cardiovascular risk including any of the following:
- - QTcF interval QTcF > 480 msec (the QT interval values must be corrected for heart
rate by Fridericia's formula [QTcF])
- Evidence of current clinically significant uncontrolled arrhythmias, including
clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd
degree atrioventricular (AV) block.
- - History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, or stenting or bypass grafting within six months
of Screening.
- - Class III or IV heart failure as defined by the New York Heart Association
functional classification system [NYHA, 1994]
- Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160
mmHg or diastolic ≥ 100 mmHg despite optimal treatment.
18. Participant has 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 chronic liver disease (including
Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of
malignancy is acceptable if otherwise meets entry criteria.
19. Presence of active renal condition (infection, requirement for dialysis or any other
condition that could affect patient's safety). Participants with isolated proteinuria
resulting from MM are eligible, provided they fulfil inclusion criteria.
20. Evidence of active mucosal or internal bleeding.
21. Use of contact lenses while participating in this study.
22. Any serious medical condition or psychiatric illness that would interfere in
understanding of the informed consent form.
23. Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or
hyperthyroidism) (i.e. requiring relevant changes in medication within the last month,
or hospital admission within the last 3 months).
24. Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
25. Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with
forced expiratory volume in the first minute (FEV1) less than 50%.
26. History of interstitial lung disease or ongoing interstitial lung disease. aa.
Participant has an active infection requiring antibiotic, antiviral, or antifungal
treatment bb. Participant has known HIV infection cc. Participant has 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.
dd. Participant has positive hepatitis C antibody test result or positive hepatitis C RNA
test result at screening or within 3 months prior to first dose of study treatment.
Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be
enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody
test are not required to also undergo Hepatitis C RNA testing.
