Belantamab Mafodotin in combination with Lenalidomide and Dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who transplant ineligible.
- Conditions
- newly diagnosed 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
- EUCTR2020-005826-27-GR
- Lead Sponsor
- Hellenic Society of Hematology (EAE)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 66
1.Participant aged 18 years or older
2.Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma and documented MM satisfying at least 1 of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:
CRAB criteria:
v.Hypercalcemia: serum calcium>0.25 mmol/L (>1 mg/dL) higher than ULN or >2.75 mmol/L(>11 mg/dL)
vi.Renal insufficiency: creatinine clearance<40mL/min or serum creatinine>177 µmol/L(>2 mg/dL)
vii.Anemia: hemoglobin>2 g/dL below the lower limit of normal or hemoglobin <10 g/dL
viii.Bone lesions: 1 or more osteolytic lesions on skeletal radiography, CT, or PET-CT
Any 1 or more of the following biomarkers of malignancy:
a.Clonal bone marrow plasma cell percentage =60%
b.Involved: uninvolved serum FLC ratio =100
c. More than 1 focal lesion on MRI studies
3.Must have at least ONE aspect of measurable disease, defined as 1 of the following:
Urine M-protein excretion=200 mg/24 hrs (=0.2g/24 hrs), or
Serum M-protein concentration =0.5 g/dL (=5.0 g/L), or
Serum FLC assay: involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
4.Not a candidate for high-dose chemotherapy with ASCT due to presence of
significant comorbid condition(s), such as cardiac, pulmonary or other major organ dysfunction that are likely to have a negative impact on tolerability of high dose
chemotherapy with stem cell transplantation. The patients will be assessed with the IMWG frailty index, a scoring system based on age, comorbidities and cognitive and physical conditions, which is recommended by the ESMO guidelines [11]. Patients with IMWG frailty index score 1 or 2 will be considered transplant ineligible. The reason(s) for transplant ineligibility will be collected in the CRFs
5.ECOG status of 0-2
6.Adequate organ system function as defined by the below laboratory assessments
Hematologic:
Absolute neutrophil count (ANC) =1.5 X 10^9/L; GCSF use is NOT allowed to reach this level
Hemoglobin = 8.0 g/dL; transfusions are permitted
Platelet count = 50 x 10^9/L if bone marrow is >50% involved in myeloma Otherwise =75 x 10^9/L; transfusions are NOT allowed to reach this level
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
Renal:
eGFR =30 mL/min/1.73 m^2; calculated using the Modified Diet in Renal Disease (MDRD) formula
Spot urine (albumin/creatinine ratio) <500 mg/g (56 mg/mmol)
OR
Urine Dipstick: Negative trace; if =1+ only eligible if confirmed <500 mg/g [56 mg/mmol] by albumin/creatinine ratio (spot urine from first void)
7.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 two methods of reliable birth control (one method that is highly effective and one additional effective [barrier] method), 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 one method of reliable birth control that is highly effective for a further 4 months following discontinuation of
1.Prior systemic therapy for MM, or smoldering MM (SMM).
2.Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute , Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 5.
3.Major surgery within 4 weeks before the first dose of study drug.
4.Presence of active renal condition (infection, requirement for dialysis or any other significant condition that could affect the participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided that they fulfil the other inclusion criteria.
5.Any serious and/or unstable pre-existing medical or, psychiatric disorder or other conditions (including laboratory abnormalities) that could interfere with participant’s safety, obtaining informed consent or compliance with the study procedures.
6.Evidence of active mucosal or internal bleeding uncontrolled by local therapy and not explained by reversible coagulopathy.
7.Current active liver or biliary disease (except for Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per the Investigator’s assessment).
8.Participants with previous or concurrent malignancies other than multiple myeloma. Exceptions are surgically treated cervical carcinoma in situ, or any other malignancy that 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.
9.Evidence of cardiovascular risk including any of the following:
•Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities, second degree (Mobitz Type II) or third degree atrioventricular (AV) block.
•History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening.
10.Class III or IV heart failure as defined by the New York Heart Association functional classification system.
11.Uncontrolled hypertension.
12.Active infection requiring treatment.
13.Known human immunodeficiency virus 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. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]).
15.Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before the first dose of the study treatment unless the participant can meet the following criteria:
•RNA test negative
•Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative hepatitis c virus (HCV) RNA test after a washout period of at least 4 weeks.
16.Current corneal epithelial disease except for mild punctate keratopathy.
17.Intolerance or contraindications to anti-viral prophylaxis.
18.Unable to tolerate antithrombotic prophylaxis.
19.AL amyloidosis (light chain amyloidosis), active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.
20.Exhibiting clinical signs of or with a known history of meningeal or central nervous system involvement by multiple myeloma.
21.Known i
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