A phase 1/2, dose and schedule evaluation study to investigate the safety and clinical activity of belantamab mafodotin administered in combination with lenalidomide, dexamethasone and nirogacestat in patients with transplant ineligible newly diagnosed multiple myeloma
- Conditions
- ewly diagnosed patients with multiple myelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-001942-39-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
- 36
1. Participants >18 of age.
2. Monoclonal plasma cells in BM =10% or presence of biopsy proven plasmacytoma and documented MM satisfying =1 of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:
CRAB criteria:
i. Hypercalcemia: serum calcium >0.25 mmol/L higher than ULN or >2.75 mmol/L.
ii. Renal insufficiency: CrCl <40mL/min or serum creatinine >177 µmol/L.
iii. Anemia: hemoglobin >2 g/dL below the LLN or hemoglobin <10 g/dL.
iv. Bone lesions: =1 osteolytic lesions on skeletal radiography, CT, or PET-CT.
Biomarkers of Malignancy:
a. Clonal BM plasma cell percentage =60%.
b. Involved:uninvolved sFLC ratio =100.
c. >1 focal lesion on MRI.
3. Must have =1 aspect of measurable disease:
o Urine M-protein excretion =200 mg/24 hrs, or
o Serum M-protein concentration =0.5 g/dL, or
o sFLC assay: involved FLC level =10 mg/dL and abnormal sFLC ratio (<0.26 or >1.65).
4. Not a candidate for high-dose chemotherapy with ASCT due to presence of significant comorbid condition(s). The patients will be assessed by the IMWG frailty index, ESMO guidelines. Patients with IMWG frailty index score 1/2 will be considered transplant ineligible.
5. ECOG PS of 0-2.
6. Adequate organ system function as defined by the below:
Hematologic
o ANC =1.25X109/L; G-CSF use for the past 14 days is NOT allowed.
o Hemoglobin =8.0 g/dL; transfusions are not permitted in the past 14 days prior to the assessment. Erythropoietin use is allowed.
o Platelet count =50x109/L if the BM is >50%. Otherwise, =75x109/L; transfusions or platelet stimulating agents are NOT allowed in the past 14 days prior to the assessment.
Hepatic
o Total bilirubin =1.5xULN (isolated bilirubin =1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
o ALT = 2.5xULN.
Renal
o eGFR =30 mL/min/1.73m2; calculated using MDRD formula.
o Spot urine (albumin/creatinine ratio) = 500mg/g
OR
o Urine Dipstick: Negative trace; if =1+ only eligible if confirmed = 500 mg/g [56 mg/mmol] by albumin/creatinine ratio.
7. Female participants: contraceptive use should be consistent with local regulations regarding methods of contraception for participants in studies:
A female is eligible if not pregnant/breastfeeding, and =1 of following:
• Not a woman of childbearing potential (WOCBP) defined as:
a. =45 age and has not had menses for >1 year.
b. Patients who have been amenorrhoeic for <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation.
c. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records.
OR
• WOCBP and using two methods of reliable birth control, beginning 4 weeks before initiating lenalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of lenalidomide. WOCBP participants must use one method of reliable birth control that is highly effective for 4 months following discontinuation of belantamab mafodotin. WOCBP must also agree not to donate eggs, during dose interruptions and for 28-days following last dose of lenalidomide or 4 months following discontinuation of belantamab mafodotin whichever is longer.
WOCBP must have two negative pregnancy tests before therapy. The first test should be performed <10-1
1. Prior systemic therapy for MM/SMM.
o NOTE 1: An emergency course of steroids permitted.
o NOTE 2: Focal palliative radiation permitted prior to enrollment, provided occurred =2 weeks before first drug, participant has recovered from radiation-related toxicities, and participant did not require corticosteroid administration for radiation-induced AEs.
2. Peripheral neuropathy or neuropathic pain =Grade 2, as defined by NCI-CTCAE V.5.
3. Major surgery within 4 weeks before first dose.
o NOTE 1: Patients who underwent major surgery must be clinically stable to be enrolled.
o NOTE 2: Major surgery shall be defined based on Investigator’s judgment.
4. Presence of active renal condition. Participants with isolated proteinuria resulting from MM are eligible, provided they meet other inclusion criteria.
5. Any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions that could interfere with participant’s safety, obtaining informed consent, or compliance to 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 Gilbert’s syndrome or asymptomatic gallstones, or otherwise stable chronic liver disease as per Investigator’s assessment).
8. Participants with previous or concurrent malignancies other than MM. Exceptions are surgically treated cervical carcinoma in situ, or other malignancy that's been considered medically stable for =2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease.
o NOTE: Participants with cured non-melanoma skin cancer are allowed without 2-year restriction.
9. Evidence of cardiovascular risk including any of:
• Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities, second degree, or third degree atrioventricular block.
• History of myocardial infarction, acute coronary syndromes, coronary angioplasty, or stenting or bypass grafting =3 months of Screening.
10. Class III/IV heart failure as defined by NYHA.
11. Uncontrolled hypertension.
12. Active infection requiring treatment.
13. Known HIV infection, unless the participant can meet all of following:
• Established ART for =4 weeks and HIV viral load <400 copies/mL.
• CD4+ T-cell (CD4+) count =350 cells/uL.
• No history of AIDS-defining opportunistic infections =12 months.
o NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products.
14. Seropositivity for hepatitis B.
o NOTE 1: Participants with resolved infection. PCR positive excluded.
o NOTE 2: Presence of antiHBs indicating previous vaccination will not be excluded.
15. Positive HCV antibody test result or positive HCV RNA test result at screening or =3 months before first dose of treatment unless participant meets the following:
• RNA test negative
• Successful anti-viral treatment required, followed negative HCV RNA test after washout period =4 weeks.
16. Current corneal epithelial disease except for mild punctate keratopathy.
o NOTE: Participants with mild punctate keratopathy allowed.
17. Intolerance or contraindications to anti-viral prophylaxis.
18. Unable to tolerate antithrombotic prophylaxis.
19. AL amyloidosis, active POEMS syndrome or active plasma cell leukemia at screening.
20. Exhib
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