Inclusion Criteria:
1. Patients with relapsed or refractory multiple myeloma. Eligible patients will be
enrolled in the protocol no less than 60 days and must be initiated no longer than 180
days (± 2 weeks) post ASCT. Patient's transplant may be either transplantation naïve
or with a history of previous autologous transplant.
2. Patients who have had two or more lines of therapy consisting of at least one of three
agents including a proteasome inhibitor or an immunomodulatory agent or an anti-CD38
targeting therapy.
Note:
a) Induction therapy, autologous stem cell transplantation (ASCT) & maintenance
therapy if given sequentially without intervening progressive disease (PD) are
considered one line of therapy. b) Refractory MM may be defined as disease that is
refractory to treatment while on therapy or that shows progression within 60 days of
the last therapy.
3. Disease status, partial response, or better.
4. Age ≥ 18-year and ≤ 75-year. English and non-English speaking patients are eligible.
5. Platelet count ≥ 50,000/mm3 & Hemoglobin ≥ 8 g/dL, ANC ≥ 1.0 × 109/L. 6. Karnofsky Performance Status (KPS) >70 (Appendix B.).
7. Adequate organ function (ALT ≤ 2.5 ULN; Total bilirubin ≤ 1.5 ULN or total bilirubin.
- - 1.5 ULN with direct bilirubin ≤ 35%; estimated glomerular filtration rate ≥30
mL/min per 1.73 m2.
8. Participants must not be pregnant or lactating. 9. Female participants: contraceptive use should be consistent with institutional
guidelines 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:
1. Is not a woman of childbearing potential (WOCBP) OR. 2. 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 (as described in Appendix
C.), 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 reproduction
during this period. The investigator should evaluate the effectiveness of the
contraceptive method in relation to the first dose of the 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 the study intervention.
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 a 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. 10. Male
participants: contraceptive use should be consistent with institutional guidelines
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 for 6 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 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 as to when having sexual intercourse with a woman of childbearing potential who
is not currently pregnant.
Exclusion Criteria:
1. Current corneal epithelial disease (except mild punctate keratopathy). 2.
Participant must not use contact lenses while participating in this study. 3. Ongoing
Grade 2 or higher peripheral neuropathy or neuropathic pain. 4. Participants who are
using an investigational drug or approved systemic anti-myeloma therapy (including
systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding
the first dose of study drug.
5. Participants who have current unstable liver or biliary disease defined by the
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia (serum albumin <
3.0 gm/dl), 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 6. Participants who have 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 inclusion criteria 7. Participants who have
received prior treatment with a monoclonal antibody within 30 days of receiving the
first dose of study drugs.
8. Participants who have had major surgery ≤ 4 weeks before initiating study
treatment.
9. Participants who have any evidence of active mucosal or internal bleeding. 10.
Participants who 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.
11. Participants who have an active infection requiring treatment 12. Participants who
have evidence of cardiovascular risk, including any of the following:
a) Evidence of current clinically significant uncontrolled and/or untreated arrhythmias,
including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or
3rd degree atrioventricular (AV) block.
b) History of myocardial infarction, acute coronary syndromes (including unstable angina),
coronary angioplasty, or stenting or bypass grafting within three
c) Class III or IV heart failure as defined by the New York Heart Association functional
classification system.
d) Uncontrolled hypertension. 13. Participants who have known HIV infection, unless the
participant can meet all of the following criteria:
- - Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400
copies/mL.
- - CD4+ T-cell (CD4+) counts ≥350 cells/uL.
- - No history of AIDS-defining opportunistic infections within the last 12 months 14.
Participant must not have 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. Note: presence of Hep B surface antibody (HBsAb) indicating
previous vaccination will not exclude a participant.
15. Participant must not have 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.
16. Participant 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. Participants with curatively treated
non-melanoma skin cancer may be enrolled without a 2-year restriction.
17. Prior allogeneic stem cell transplant. NOTE: Participants who have undergone syngeneic
transplant will be allowed only if no history of or no currently active GvHD.
18. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal plasmaproliferative disorder, skin changes) or active plasma
cell leukaemia at the time of screening.
19. Patients with cognitive impairments and/or any serious unstable pre-existing medical
condition or psychiatric disorder that can interfere with safety or with obtaining informed
consent or compliance with study procedures. Informed Consent Process. The informed consent
process will begin at recognition of subject eligibility, and consent will be obtained per
Institutional practices before study therapy is initiated.
