A study of belantamab mafodotin compared to a combination of pomalidomide and dexamethasone in participants with relapsed/refractory multiple myeloma
- Conditions
- Relapsed/Refractory Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004252-38-HU
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 325
1. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with requirements and restrictions listed in
the 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 (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 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 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 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 [Appendix 4] OR
• Is a WOCBP and agrees to abide by the following:
• Arm 1 (belantamab mafodotin): Use a contraceptive method that is highly effective (with a failure rate of <1% per year) which includes abstinence, preferably with low user dependency during the intervention period and for 4 months after the last dose of study treatment.
• Arm 2 (pom/dex): Due to pomalidomide being a thalidomide analogue with risk for embryofetal
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.
18. Known human immunodeficiency virus (HIV), unless the participant can meet all of the following criteria:
• Established anti-retroviral therapy (ART) for at least 4 weeks and HIV
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method