A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Single Agent Belantamab Mafodotin Compared to Pomalidomide plus Low-dose Dexamethasone (pom/dex) in Participants with Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 3)
- Conditions
- Kahler's diseaseMultiple Myeloma10035227
- Registration Number
- NL-OMON52689
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
1. Capable of giving signed informed consent as described in Protocol
Appendix 1 which includes compliance with the requirements and
restrictions listed in the informed consent form (ICF) and in the protocol.
2. Participants must be 18 or older, at the time of signing the ICF.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0
to 2 (Protocol Appendix 9).
4. Histologically or cytologically confirmed diagnosis of multiple
myeloma (MM) as defined according to International Myeloma Working
Group (IMWG), and:
a. Has undergone autologous stem cell transplant (SCT), or is considered
transplant ineligible, and
b. 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 i) Must have
documented disease progression on, or within 60 days of, completion of the last
treatment OR (ii) Must be non-responsive while on last treatment, where
non-responsive is defined as not achieving at least Minimal Response (MR) after
2 complete treatment cycles. In such cases lack of achieving of at least MR
must be determined no earlier than at least 4 weeks after the last treatment.
5. Has measurable disease with at least one of the following:
a. Serum M-protein >=0.5 g/dL (>=5 g/L)
b. Urine M-protein >=200 mg/24 hours
c. Serum free light chain (FLC) assay: Involved FLC level >=10 mg/dL (>=
100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
6. Participants with a history of autologous SCT are eligible for study
participation provided the following eligibility criteria are met:
a. Transplant was >100 days prior to initiating study treatment
b. No active infection(s)
c. Participant meets the remainder of the protocol eligibility criteria
7. Adequate organ system functions as defined in Protocol Table 9
8. Contraceptive use by men or women should be consistent with local
regulations regarding the methods of contraception for those
participating in clinical studies.
a. Male Participants:
Male participants are eligible to participate if they agree to the following
during the intervention period and until 6 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 a male condom throughout study treatment
including the 6 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% per year as
described in Protocol Appendix 4 when having sexual intercourse with a
pregnant woman or a woman of childbearing potential (WOCBP) who is
not currently pregnant.
*4 weeks for male participants on Treatment Arm 2 (pom/dex).
b. Female Participants:
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 WOCBP [Protocol Appendix 4]
OR
• Arm 1 (belantamab mafodotin): Use a contraceptive method that is
highly effective (with a failure rate of <1% per year) which includes
absti
1. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, myeloma protein, and skin changes);
active plasma cell leukemia at the time of screening.
2. 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.
3. Prior treatment with an anti-MM monoclonal antibody within 30 days
prior to receiving the first dose of study intervention.
4. Prior BCMA-targeted therapy or prior pomalidomide treatment.
5. Plasmapheresis within 7 days prior to the first dose of study
intervention.
6. Prior allogeneic stem cell transplant.
NOTE - Participants who have undergone syngeneic transplant will be
allowed only if no history of, or currently active GvHD.
7. Any major surgery within the last 4 weeks.
8. 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 included in Table 9 of the protocol.
9. 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.
10. History of (non-infectious) pneumonitis that required steroids, or
current pneumonitis.
11. Evidence of active mucosal or internal bleeding.
12. Current unstable liver or biliary disease per investigator assessment
defined by the presence of ascites, encephalopathy, coagulopathy,
hypoalbuminemia, oesophageal 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.
13. 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. NOTE - Participants with curatively treated non-melanoma skin
cancer are allowed without a 2-year restriction.
14. Evidence of cardiovascular risk including any of the following:
a. QT interval corrected for heart rate by Fridericia's formula (QTcF) >=
480 msec
b. Evidence of current clinically significant uncontrolled arrhythmias
including clinically significant electrocardiogram (ECG) abnormalities
including 2nd degree (Mobitz Type II) or 3rd degree atrioventricular
block.
c. History of myocardial infarction, acute coronary syndromes (including
unstable angina), coronary angioplasty, or stenting or bypass grafting
within 3 months of Screening.
d. Class III or IV heart failure as defined by the New York Heart
Association (NYHA) functional classification system (Appendix 10 of the
protocol)
e. Uncontrolled hypertension.
15. 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.
16. Pregnant or lactating female.
17. Active infection requiring treatment.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS, defined as the time from the date of randomization until the earliest date<br /><br>of documented disease progression (according to IMWG Response<br /><br>Criteria) or death due to any cause</p><br>
- Secondary Outcome Measures
Name Time Method