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

NCT05055063 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0431NCI-2021-08991
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloma

Outcome Measures

Primary Outcomes (1)

• To establish the recommended Phase 2 dose (RP2D) or maximum tolerated dose of single agent belantamab mafodotin in high risk SMM.

  through study completion, an average of 1 year

Study Arms (1)

Belantamab mafodotin

EXPERIMENTAL

belantamab mafodotin by vein over 30-60 minutes on Day 1 of each 56-day cycle for the first 6 cycles.

Drug: Belantamab mafodotin

Interventions

Belantamab mafodotin DRUG

by vein over 30-60 minutes on Day 1 of each 56-day cycle for the first 6 cycles.

Belantamab mafodotin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Females of childbearing potential are eligible to participate if they agree to notdonate eggs (ova, oocytes) for the purpose of reproduction during the study and for 4 months after the last dose of belantamab mafodotin.
• Male participants are eligible to participate if they agree to the following from the time of first dose of belantamab mafodotin until 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
• be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent,
• OR must agree to use contraception/barrier as follows:
• agree to use a male condom, even if they have undergone a successful vasectomy

You may not qualify if:

• 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.
• Radiotherapy is not permitted.
• Prior or concurrent treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of smoldering multiple myeloma
• Plasma cell leukemia
• Pregnant or lactating females. It is not known whether belantamab mafodotin is excreted in human milk. The effect of belantamab mafodotin of newborns/infants is unknown. Women should be advised to discontinue breast-feeding prior to initiating treatment with belantamab mafodotin and for at least 70 days after the last dose. These potential risks may also apply to other agents used in this study.
• Active hepatitis B or C infection

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

belantamab mafodotin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Study Officials

• Robert Orlowski

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Astrid Murga

CONTACT

713-792-3664; ADMurga@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 23, 2021
• Study Start: May 18, 2022
• Primary Completion (Estimated): February 2, 2027
• Study Completion (Estimated): February 2, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (1)