A Phase 1 With Extension Cohort, Single Arm, Single Center, Open Label Trial of Belantamab Mafodotin for the Treatment of High-Risk Smoldering Multiple Myeloma (BELLA)
Overview
- Phase
- Phase 1
- Intervention
- Belantamab mafodotin
- Conditions
- Myeloma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- To establish the recommended Phase 2 dose (RP2D) or maximum tolerated dose of single agent belantamab mafodotin in high risk SMM.
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a single-center, single arm, phase I study designed to determine the safety and find the recommended Phase 2 dose (RP2D) or maximum dose level (MTD) of Belantamab Mafodotin in patients with high-risk smoldering multiple myeloma. The study will have a dose-finding part and a dose-expansion part. The maximum number of enrolled patients will be 30 with 18 patients for the dose-finding part and 12 patients for the dose-expansion part. Once we determine the MTD or RP2D in the dose-finding part, we will enroll and treat 12 additional patients at the MTD or RP2D in the expansion part. Efficacy will be assessed through the overall response rate (ORR) at the end of the study. With the limited number of patients for the dose-expansion part, we will not have formal futility monitoring rule.
Detailed Description
Primary Objective: To obtain the recommended Phase 2 dose (RP2D) or maximum tolerated dose of single agent belantamab mafodotin in high risk SMM. Secondary Objectives: Overall response rate per International Myeloma Working Group (IMWG) criteria. Progression free survival at 2 years, overall survival, duration of response, safety and clinical benefit rate. Exploratory Studies: Evaluate correlative endpoints including immune, cellular and molecular profiling, minimal residual disease, BCMA staining of bone marrow, pharmacokinetics, pharmacodynamics and mechanisms of resistance to belantamab mafodotin.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must be diagnosed with high-risk smoldering multiple myeloma (SMM) as confirmed by the following (all three must be present):
- •Bone marrow plasmacytosis with ≥ 10% plasma cells in bone marrow biopsy
- •Immunoparesis (reduction in at least one uninvolved immunoglobulin in blood)
- •≥ 95% aberrant plasma cells of all plasma cells by flow cytometry of the bone marrow aspirate
- •Creatinine clearance (CrCl) ≥ 30 ml/min. CrCl will be calculated using the Modification of Diet in Renal Disease (MDRD) equation.
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L, hemoglobin more or equal than 2 grams below the institutional level of normal and platelet count ≥ 90 x 109/L. Platelet and blood transfusions are allowed on protocol. Growth factors, including granulocyte colony stimulating factors and erythropoietin are allowed.
- •Adequate hepatic function, with bilirubin ≤ 1.5 x the ULN, and AST and ALT ≤ 2.5 x ULN.
- •Females of childbearing potential are eligible to participate if they agree to avoid pregnancy by using an adequate method of contraception that is highly effective with a failure rate of \<1% per year (2 barrier method or 1 barrier method with a spermicide or intrauterine device during and for 4 months after the last dose of belantamab mafodotin). Adequate methods of contraception are provided as examples. Other acceptable and effective methods of birth control are also permitted (eg, abstinence). Women of child bearing potential must have a negative serum pregnancy test result within 72 hours prior to the first administration of belantamab mafodotin and at the end of treatment visit. A negative urine pregnancy test is required prior to each subsequent belantamab mafodotin dose administration
Exclusion Criteria
- •Evidence of myeloma defining events or biomarkers of malignancy due to underlying plasma cell proliferative disorder meeting at least one of the following:
- •Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\> 11 mg/dL)
- •Renal Insufficiency: creatinine clearance \< 40 ml/min or serum creatinine \> 2 mg/dL
- •Anemia: hemoglobin value more than 2 g/dL \< normal reference
- •Bone lesions: one or more osteolytic lesions on skeletal radiography, computerized tomography (CT) or 2-deoxy-2\[F-18\] fluoro-D-glucose positron emission tomography CT (PET-CT).
- •Clonal bone marrow plasma cell percentage ≥ 60%
- •Involved: uninvolved serum free light chain ratio ≥100 measured by Freelite assay (The Binding Site Group, Birmingham, UK)
- •\>1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size)
- •Bisphosphonates are permitted, including pamidronate, zoledronic acid, alendronate, ibandronate, risedronate.
- •Treatment with corticosteroids is not permitted, unless the patient is on a stable chronic dose of inhaled steroids to treat respiratory diseases or on stable chronic steroid replacement therapy for endocrinology disorders. Steroids may be used treat infusion related reactions. Inhaled, intranasal, and topical ophthalmic steroids are not prohibited.
Arms & Interventions
Belantamab mafodotin
belantamab mafodotin by vein over 30-60 minutes on Day 1 of each 56-day cycle for the first 6 cycles.
Intervention: Belantamab mafodotin
Outcomes
Primary Outcomes
To establish the recommended Phase 2 dose (RP2D) or maximum tolerated dose of single agent belantamab mafodotin in high risk SMM.
Time Frame: through study completion, an average of 1 year