Multiple myeloma Cancer Multiple Myeloma
Conditions
Interventions
Current interventions as of 04/02/2025:
This is a multi-centre, multi-arm, phase I platform study in relapsed/refractory multiple myeloma patients with 1-4 prior lines of therapy. The trial includes m
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Age
18 Years to 110 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 04/02/2025: 1. Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined according to International Myeloma Working Group (IMWG) criteria 2. Relapsed or refractory disease, having received between 1 and 3 prior lines of therapy which include a proteasome inhibitor (including bortezomib, carfilzomib, ixazomib) and an immunomodulatory imide drug (including thalidomide, lenalidomide, pomalidomide). 3. Have measurable disease with at least one of the following: - Paraprotein =5 g/l - Serum free light chains =100 mg/l with abnormal ratio for light chain only myeloma - Bence Jones protein = 200 mg/day OR - Non-secretory/ Oligosecretory disease defined within this protocol as =30% neoplastic plasma cells in the bone marrow 4. Aged =18 years on day of signing informed consent 5. Not pregnant or breastfeeding, and one of the following conditions applies: 5.1. Not a woman of childbearing potential (WOCBP) 5.2. Is a WOCBP and all of the following apply: 5.2.1. Is using a highly effective (with a failure rate of <1% per year) method of contraception (preferably with low user dependency) from 4 weeks prior to the start of treatment, during the intervention period, and for the contraceptive time frame specified in the arm-specific eligibility criteria. 5.2.2. Have a negative urine or serum pregnancy test as outlined in each treatment sub-protocol and agree to use a highly effective method of contraception from 4 weeks prior to the start of treatment, during the study, and for 9 months after the last dose of belamaf 5.2.3. Have agreed not to donate eggs (ova, oocytes) for the purpose of reproduction during this period 6. Male participants of childbearing potential who agree to one of the following from the time of dosing on C1D1 until 6 months after the last dose of study treatment, to allow for clearance of any altered sperm: 6.1. Abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), or agree to use a male condom (even if they have undergone a successful vasectomy) 6.2. If applicable, WOCBP (including pregnant females) partners to use an additional highly effective contraceptive method with a failure rate of <1% per year 6.3 Refrain from donating sperm during this period 7. Agree to refrain from donating blood while on trial drug, including during dose interruptions and for 120 days after discontinuation from this trial 8. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03), except for alopecia, must be =Grade 1 at the time of enrolment 9. Adequate organ function as defined by the following assessments: - Absolute neutrophil count (ANC) =1 X 109/L - Haemoglobin =80 g/l - Platelets =75 x10?/l - Total bilirubin =1.5 x ULN - ALT =2.5 x ULN 10. Calculated creatinine clearance =40 ml/min/1.73 m² using Cockcroft-Gault formula 11. Spot urine <500 mg/g 12. ECOG Performance Status between grade 0-2 _____ Previous inclusion criteria as of 07/11/2023: 1. Histologically or cytologically confirmed diagnosis of multiple myeloma (MM) as defined according to International Myeloma Working Group (IMWG) criteria 2. Relapsed or refractory disease, having received between 1 and 3 prior lines of therapy which include a proteasome inhibitor (including bortezomib, carfilzomib, ixazomib) and an immunomodulatory imide drug (including thalido
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 04/02/2025: 1. Non-measurable disease (does not meet Inclusion Criteria 3), solitary bone or solitary extramedullary plasmacytoma, plasma cell leukaemia, POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), systemic amyloidosis 2. Currently participating and receiving trial therapy or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 28 days prior to dose allocation 3. Any of the following prior treatments: 3.1. Autologous stem cell transplantation 530 msec based on average value of triplicate ECGs performed within 14 days of registration 5. Prior treatment with a B-cell maturation antigen (BCMA) targeted therapy 6. Current corneal epithelial disease except for mild changes in corneal epithelium 7. Requirement to wear contact lenses 8. Active renal condition (infection, requirement for dialysis, or any other condition that could affect participant’s safety) or unstable liver or biliary disease (defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis) per investigator assessment. Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria. 9. Known history of Human Immunodeficiency Virus (HIV) 10. Known active Hepatitis B or Hepatitis C confirmed by antibody test or RNA test within 3 months prior to dose allocation. 11. Any major surgery within 4 weeks prior to dose allocation. 12. Active infection requiring systemic antibiotic, antiviral, or antifungal treatment within 7 days of dose allo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose finding phase: 1. Dose limiting toxicities within the first cycle of treatment measured using measured using adverse event collection and safety assessments between 0 and 28 days Expansion phase: 1. Participant response assessed using the proportion of participants achieving at least a very good partial response (VGPR) whilst on trial treatment using International Myeloma Working Group (IMWG) criteria at the beginning of each cycle up from baseline until disease progression or stopping 2. Safety and toxicity measured using adverse events, graded using the Common Terminology Criteria for Adverse Events (CTCAE version 5.0), Serious Adverse Events (SAEs), Serious Adverse Reactions (SARs), and Serious Unexpected Serious Adverse Reactions (SUSARs), and determined by routine assessments at each site from 0 days until disease progression or stopping | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall response rate measured from response assessments, using IMWG criteria, at the beginning of each cycle up from baseline until disease progression or stopping 2. MRD negativity rate measured using IMWG criteria from bone marrow samples taken at 6, 12 and 18 months 3. Progression-free survival measured as the time from registration to first documented evidence of disease progression or death, where response is measured at the beginning of each cycle and diseases progression 4. Maximum response measured from response assessments, using IMWG criteria, at the beginning of each cycle up from baseline until disease progression or stopping 5. Time to maximum response measured from response assessments, using IMWG criteria, at the beginning of each cycle from baseline up until disease progression 6. Duration of response measured from response assessments, using IMWG criteria, at the beginning of each cycle from baseline up until disease progression 7. Compliance to therapy measured using dosing information (such as dose omission, delays, modifications) reported after each cycle of treatment from baseline until disease progression or stopping 8. Quality of life measured using the Myeloma-Specific Quality of Life Questionnaire (MyPOS) at baseline, once every 3 cycles during treatment (starting at C3D1), at end of treatment, and then during post-treatment follow-up at each ophthalmology appointment the participant undergoes for eye toxicity | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactHeena Patel
Outcome results
None listed