newly diagnosed multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Hellenic Society of Hematology (EAE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 clearance177 µmol/L(>2 mg/dL) vii.Anemia: hemoglobin>2 g/dL below the lower limit of normal or hemoglobin 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 – Dose finding To determine the safety and tolerability of Belantamab mafodotin in combination with lenalidomide and dexamethasone to establish an RP2D for participants with TI NDMM. Part 2 – Dose expansion To further evaluate the safety and determine the preliminary clinical activity of belantamab mafodotin RP2D in combination with lenalidomide and dexamethasone.;Secondary Objective: To evaluate the effect of combining belantamab mafodotin with lenalidomide and dexamethasone: Assess the efficacy of belantamab mafodotin in combination with lenalidomide and dexamethasone in TI NDMM. Evaluate alternate corneal AE management approach using Alternate Dose Modification Guidelines for belantamab mafodotin-related ocular adverse events. To further characterize the pharmacokinetic (PK) profile of belantamab mafodotin when administered in combination with lenalidomide and dexamethasone. To evaluate symptomatic AEs measured by the Ocular Surface Disease Index (OSDI) questionnaire as documented by the investigator. •To evaluate Vision-related functioning measured by the Vision Related Anamnestic Tool as documented by the investigator Exploratory Objectives: To investigate the relationship between biological characteristics and clinical response. To explore the exposure-response relationship of belantamab mafodotin exposure with clinical endpoints ;Primary end point(s): Part 1 Number of participants with dose-limiting toxicities (DLTs). Number of participants with adverse events (AEs) and serious adverse events (SAEs). Part 2 Overall Response rate as per International Myeloma Working Group (IMWG) by Investigator Assessment. Number of participants with adverse events (AEs) and serious adverse events (SAEs).;Timepoint(s) of evaluation of this end point: DLTs will be evaluated during the first cycle of study treatment (4 weeks) Remaining endoipints: During the whole study duration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 & 2 Lenalidomide relative Dose Intensity (RDI). Cumulative administered dose of belantamab mafodotin in combination with lenalidomide and dexamethasone (Rd) Time to Response (TTR) as per IMWG by Investigator Assessment. Duration of Response (DoR) as per IMWG by Investigator Assessment. Complete Response Rate (CRR) as per IMWG by Investigator Assessment. MRD negativity rate in the bone marrow (BM), defined as the number (%) of participants who achieve MRD negativity (at or below the threshold of 10-5), assessed via NGF. MRD will be assessed via next-generation flow (NGF) cytometry. Progression Free Survival (PFS) as per IMWG by Investigator Assessment. Overall Survival (OS). Number of participants with abnormal ocular findings (on ophthalmic exam). Derived PK parameter values for belantamab mafodotin ADC. Number of participants with changes from baseline and proportion of participants with within-participant meaningful change in self reported ocular symptoms and related impacts as measured by the OSDI questionnaire (Part 1 only). Number of participants with changes from baseline and proportion of participants with within-participant meaningful change in ocular symptoms and related impacts as measured by the Vision Related Anamnestic Tool (Part 2 only) Exploratory Endpoints Part 1 & 2 Relation between baseline bone marrow B-cell maturation antigen (BCMA) expression levels/soluble BCMA (sBCMA) levels AND clinical response. Change from baseline of sBCMA levels. Belantamab mafodotin exposure (e.g., concentration, Cmax, or AUC) vs. efficacy and/or safety endpoints (e.g., ORR, CRR, ocular events), as data permit ;Timepoint(s) of evaluation of this end point: During the whole study duration | — |
Countries
Greece
Contacts
Public ContactEAE - Prof. Evangelos Terpos
Hellenic Society of Hematology (EAE)
Outcome results
None listed