study to evaluate the safety of the study drug, GSK2857916, at different doses and how well it works to treat people with multiple myeloma when taken together with Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm B).
- Conditions
- Relapsed / Refractory Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-004689-93-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 152
1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Male or female, 18 years or older (at the time consent is obtained).
3. Have confirmed diagnosis of Multiple Myeloma as defined by the International Myeloma Working Group (IMWG)[Rajkumar, 2016].
4. Eastern Cooperative Oncology Group (ECOG) performance status:
? -For Arm A only: 0 to 1 (Appendix 3, Section 13.3 in the Protocol).
? -For Arm B only: 0 to 2 (Appendix 3, Section 13.3 in the Protocol).
5. Have undergone autologous SCT or are considered transplant ineligible.
6. Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy.
7. Must have at least ONE aspect of measurable disease, defined as one of the following:
a. Urine M-protein excretion =200 mg/24h, or
b. Serum M-protein concentration =0.5 g/dL (=5.0 g/L), or
c. Serum free light chain (FLC) assay: involved FLC level =10 mg/dL
(=100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).
8. Participants with a history of autologous stem cell transplant (SCT) are eligible for study participation provided the following eligibility criteria are met:
a. Autologous SCT was >100 days prior to study enrollment
b. No active bacterial, viral, or fungal infection(s) present
c. Participant meets the remainder of the eligibility criteria outlined in this protocol
9. All prior treatment-related toxicities (defined by National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be Grade =1 at the time of enrollment, except for alopecia. Participants with Grade 2 neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex treatment arm.
10. Adequate organ system functions as defined by laboratory assessments listed in Table 13 in the Protocol.
(For Inclusion Criteria related with Female and Male Participants
Contraception, please refer to the Protocol)
Additional Inclusion Criteria for WOCBP Participants Assigned to Arm A Due to lenalidomide being a thalidomide analogue with risk for embryofetal toxicity and prescribed under a pregnancy prevention/controlled distribution program, WOCBP participants will be eligible if they commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control (one method that is highly effective), beginning 4 weeks prior to initiating treatment with lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants must use a contraceptive method that is highly effective (with a failure rate of <1% per year) for a further 3 months, and agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period.
Two negative pregnancy tests must be obtained prior to initiating lenalidomide therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing lenalidomide therapy.
Additional Inclusion Criteria for WOCBP Participants Assigned to Arm B WOCBP assigned to Arm B must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1 and agree to use effective contraception during the study and for 4 months after the last dose of belantamab mafodotin or 7 months from
1. Systemic anti-myeloma therapy (including systemic steroids) within = 14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
2. Use of an investigational drug within 14 days or five half-lives (whichever is longer) preceding the first dose of study drug.
3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs.
4. Prior allogenic stem cell transplant.
Note: Participants who have undergone syngeneic transplant will be allowed only if they have no history and no currently active, graft versus host disease (GvHD)
5. Evidence of active mucosal or internal bleeding.
6. Any major surgery within the last four weeks.
7. 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 fulfill criteria given in Table 8 in the Protocol
8. 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 to the study procedures.
9. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease per investigator’s assessment).
10. Participants with invasive 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.
11. Evidence of cardiovascular risk including any of the following:
a. Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities including 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 3 months of Screening.
c. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 5, Section 13.5 in the Protocol).
d. Uncontrolled hypertension.
12. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment.
13. Pregnant or lactating female.
14. Active infection requiring treatment.
15. Known HIV infection.
16. 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)
17. 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. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing
18. Current corneal disease except for mild punctate keratopathy (Appendix 8, Section 13.8 in the Protocol). Note: Participants with mild punctate keratopathy are allowed.
Addi
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