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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

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ClinicalTrials.gov Identifier: NCT05055063
Recruitment Status : Recruiting
First Posted : September 23, 2021
Last Update Posted : May 25, 2022
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Myeloma Drug: Belantamab mafodotin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 18, 2022
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Belantamab

Arm Intervention/treatment
Experimental: Belantamab mafodotin
belantamab mafodotin by vein over 30-60 minutes on Day 1 of each 56-day cycle for the first 6 cycles.
Drug: Belantamab mafodotin
by vein over 30-60 minutes on Day 1 of each 56-day cycle for the first 6 cycles.




Primary Outcome Measures :
  1. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must be diagnosed with high-risk smoldering multiple myeloma (SMM) as confirmed by the following (all three must be present):

  1. Bone marrow plasmacytosis with ≥ 10% plasma cells in bone marrow biopsy
  2. Immunoparesis (reduction in at least one uninvolved immunoglobulin in blood)
  3. ≥ 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
      • and female partner of childbearing potential to use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse.
    • Men must agree to not donate sperm while on the study and for at least 6 months after the last dose of belantamab mafodotin.
    • Subjects must be able to give informed consent.
    • Subjects must be either newly diagnosed smoldering myeloma or not have received prior or concurrent treatment for smoldering multiple myeloma with chemotherapy agents approved for the treatment of smoldering multiple myeloma. Patients who have been treated previously on a clinical trial or with non-approved agents for their smoldering myeloma can be included.
    • 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.
    • 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
    • Known HIV infection
    • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin
    • Concurrent treatment with other anti-cancer therapy is not permitted
    • Has significant cardiovascular disease with:

      • NYHA Class III or IV symptoms,
      • uncontrolled hypertension
      • hypertrophic cardiomyopathy restrictive cardiomyopathy, or myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months prior to enrollment
      • evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block as determined by history and physical examination.
    • Uncontrolled intercurrent illness including but not limited to active infection requiring treatment or psychiatric illness/social situations that would compromise compliance with study requirements
    • Contraindication to any concomitant medication, including pre-medications or hydration given prior to therapy
    • Major surgery within 1 month prior to enrollment
    • Previous or concurrent malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction.
    • Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting are eligible, provided they fulfil renal criteria provided above.
    • Any evidence of active mucosal or internal bleeding
    • Received prior treatment with a monoclonal antibody within 30 days of receiving the first dose of belantamab mafodotin
    • Cirrhosis or current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: 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
    • Current corneal epithelial disease except mild changes in corneal epithelium
    • Use of contact lenses while participating in this study, except at the direction of the study MD/OD
    • Severe dry eye patients and monocular patients are excluded

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05055063


Contacts
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Contact: Lisa Aoula 713-563-4898 lladkins@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Lisa Aoula    713-563-4898    lladkins@mdanderson.org   
Principal Investigator: Elisabet Manasanch, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Elisabet Manasanch M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT05055063    
Other Study ID Numbers: 2020-0431
NCI-2021-08991 ( Other Identifier: NCI-CTRP Registry Program )
First Posted: September 23, 2021    Key Record Dates
Last Update Posted: May 25, 2022
Last Verified: May 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Hypergammaglobulinemia