RECRUITING

Alternate Doses and Dosing Schedules of Belantamab Mafodotin for Treatment of Triple-Class Refractory Multiple Myeloma

Conditions

Recurrent Multiple Myeloma Refractory Multiple Myeloma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial tests alternate doses and dosing schedules of belantamab mafodotin in treating patients with triple-class multiple myeloma that has come back (after a period of improvement) (recurrent) and/or does not respond to treatment (or that has not responded to previous treatment) (refractory). Belantamab mafodotin is a monoclonal antibody, belantamab, linked to a chemotherapy drug, mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. This trial may help researchers determine if alternate doses and dosing schedules work better in preventing certain side effects, such as eye toxicity, and treating patients with recurrent or refractory multiple myeloma.

Official Title

Phase II Trial for Evaluation of Alternate Doses and Dosing Schedules of Belantamab Mafodotin in Triple-Class Refractory Multiple Myeloma

Quick Facts

Study Start:2024-01-04

Study Completion:2027-05-29

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05847569

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age \>= 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2 * Histologically or cytologically confirmed diagnosis of multiple myeloma (MM), as defined in International Myeloma Working Group (IMWG) criteria, and: * If patients have undergone stem cell transplantation (SCT), day 0 of SCT must be \> 100 days prior to registration to be eligible for the study * Has had disease progression after \>= 3 prior lines of anti-myeloma treatments including one proteasome inhibitor (eg. bortezomib, carfilzomib or ixazomib), one immunomodulatory agent (eg.thalidomide, lenalidomide or pomalidomide) and one anti-CD38 monoclonal antibody (eg.daratumumab or isatuximab) * Prior non-belantamab mafodotin anti-BCMA agent exposure is allowed; patients with prior treatment with an anti-BCMA chimeric antigen receptor (CAR)-T or bispecific antibody will be allowed to participate in the study * Has measurable disease with at least one of the following: * Serum M-protein \>= 0.5 g/dL (\>= 5 g/L) * Urine M-protein \>= 200 mg/24 h * Serum free light chain (FLC) assay: Involved FLC level \>= 10 mg/dL (\>= 100 mg/L) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65) * Note: Patients with non-secretory disease will be allowed to participate * Absolute neutrophil count \>= 0.75 x 10\^9/L (=\< 28 days prior to registration) * Without growth factor support, blood transfusion, or platelet stimulating agents for the past 14 days, excluding erythropoietin * Hemoglobin \>= 7.0 g/dL (=\< 28 days prior to registration) * Without growth factor support, blood transfusion, or platelet stimulating agents for the past 14 days, excluding erythropoietin * Platelets \>= 50 x 10\^9/L (=\< 28 days prior to registration) * Without growth factor support, blood transfusion, or platelet stimulating agents for the past 14 days, excluding erythropoietin * Total bilirubin =\< 2.0 x upper limit of normal (ULN) (=\< 28 days prior to registration); (Isolated bilirubin \>= 2.0 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \< 35%) * Alanine aminotransferase =\< 2.5 x ULN (=\< 28 days prior to registration) * Aspartate transaminase =\< 2.5 x ULN (=\< 28 days prior to registration) * Estimated glomerular filtration rate (eGFR) \>= 30 mL/min/1.73 m\^2 (=\< 28 days prior to registration) * As calculated by Modification of Diet in Renal Disease (MDRD) formula * Spot urine (albumin/creatinine ratios \[spot urine\]) =\< 500 mg/g (56 mg/mmol) OR urine dipstick negative/trace (if \>1+ only eligible if confirmed =\< 500 mg/g \[56 mg/mmol\] by albumin/creatinine ratio \[spot urine from first void\]) (=\< 28 days prior to registration) * Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only. Both females and males must agree to follow the instructions * NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Provide written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the study protocol * Willingness to provide mandatory blood specimens for correlative research * Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)	* Active plasma cell leukemia at the time of screening. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, myeloma protein, and skin changes), Waldenstrom Macroglobulinemia * The only exception is emergency use of a short course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40 mg/day for a maximum of 4 days) before treatment * Prior belantamab mafodotin therapy. However, patients with prior exposure to another non-belantamab mafodotin anti-BCMA agent such as an anti-BCMA CAR-T or anti-BCMA bispecific antibody will be allowed to participate in the study * Systemic active infection requiring treatment * Any unresolved toxicity \>= grade 2 from previous treatment except for alopecia, or peripheral neuropathy up to grade 2 * Any major surgery =\< 4 weeks prior to registration * Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities except renal impairment) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures * Evidence of active mucosal or internal bleeding * Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria * Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the prior malignancy has been considered medically stable for \> 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. NOTE: Participants with curatively treated nonmelanoma skin cancer are allowed without a 2-year restriction. * Evidence of cardiovascular risk, including any of the following: * Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz type II) or 3rd degree atrioventricular (AV) block * History of myocardial infarction (=\< 6 months), acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 12 weeks of screening * Class III or IV heart failure as defined by the New York Heart Association functional classification system \[NYHA, 1994\] * Uncontrolled hypertension * Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment * Known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria: * Established anti-retroviral therapy (ART) for at \>=4 weeks and HIV viral load \< 400 copies/mL * CD4+ T-cell (CD4+) counts \>= 350 cells/uL * No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections \< 12 months prior * 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 as relevant * Patients with hepatitis B will be excluded unless the following criteria can be met: * If patient's serology shows hepatitis B virus core antibody (HbcAb)+ and hepatitis B surface antigen (HbsAg)-, they must have undetectable hepatitis B virus (HBV) deoxyribonucleic acid (DNA) at screening. Patients will be monitored per protocol. Antiviral treatment would be instituted if HBV DNA becomes detectable * If patient's serology shows HBsAg+ at screen or within 3 months prior, patients must have undetectable HBV DNA at screening, must have started highly effective antiviral treatment at least 4 weeks prior to registration, and must have baseline imaging per protocol (patients with cirrhosis are excluded). Patients must remain on antiviral treatment throughout the study. Patients will be monitored per protocol * Note: presence of hepatitis (Hep) B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant. * Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or =\< 12 weeks prior to first dose of study treatment unless the participant can meet the following criteria: * RNA test negative * Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period \>= 4 weeks * Current corneal epithelial disease except for mild punctuate keratopathy * Participant who received plasmapheresis within =\< 7 days prior to registration * Patients who received prior allogeneic stem cell transplant * Participant who received a live or live-attenuated vaccine =\< 30 days prior to registration. Ok to receive coronavirus disease (COVID) vaccine at any timepoint during protocol treatment * Participant is a woman who is pregnant or lactating * Participant who plans on wearing contact lenses during treatment with belantamab mafodotin

Inclusion Criteria

Exclusion Criteria

* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
* Histologically or cytologically confirmed diagnosis of multiple myeloma (MM), as defined in International Myeloma Working Group (IMWG) criteria, and:
* If patients have undergone stem cell transplantation (SCT), day 0 of SCT must be \> 100 days prior to registration to be eligible for the study
* Has had disease progression after \>= 3 prior lines of anti-myeloma treatments including one proteasome inhibitor (eg. bortezomib, carfilzomib or ixazomib), one immunomodulatory agent (eg.thalidomide, lenalidomide or pomalidomide) and one anti-CD38 monoclonal antibody (eg.daratumumab or isatuximab)
* Prior non-belantamab mafodotin anti-BCMA agent exposure is allowed; patients with prior treatment with an anti-BCMA chimeric antigen receptor (CAR)-T or bispecific antibody will be allowed to participate in the study
* Has measurable disease with at least one of the following:
* Serum M-protein \>= 0.5 g/dL (\>= 5 g/L)
* Urine M-protein \>= 200 mg/24 h
* Serum free light chain (FLC) assay: Involved FLC level \>= 10 mg/dL (\>= 100 mg/L) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
* Note: Patients with non-secretory disease will be allowed to participate
* Absolute neutrophil count \>= 0.75 x 10\^9/L (=\< 28 days prior to registration)
* Without growth factor support, blood transfusion, or platelet stimulating agents for the past 14 days, excluding erythropoietin
* Hemoglobin \>= 7.0 g/dL (=\< 28 days prior to registration)
* Without growth factor support, blood transfusion, or platelet stimulating agents for the past 14 days, excluding erythropoietin
* Platelets \>= 50 x 10\^9/L (=\< 28 days prior to registration)
* Without growth factor support, blood transfusion, or platelet stimulating agents for the past 14 days, excluding erythropoietin
* Total bilirubin =\< 2.0 x upper limit of normal (ULN) (=\< 28 days prior to registration); (Isolated bilirubin \>= 2.0 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \< 35%)
* Alanine aminotransferase =\< 2.5 x ULN (=\< 28 days prior to registration)
* Aspartate transaminase =\< 2.5 x ULN (=\< 28 days prior to registration)
* Estimated glomerular filtration rate (eGFR) \>= 30 mL/min/1.73 m\^2 (=\< 28 days prior to registration)
* As calculated by Modification of Diet in Renal Disease (MDRD) formula
* Spot urine (albumin/creatinine ratios \[spot urine\]) =\< 500 mg/g (56 mg/mmol) OR urine dipstick negative/trace (if \>1+ only eligible if confirmed =\< 500 mg/g \[56 mg/mmol\] by albumin/creatinine ratio \[spot urine from first void\]) (=\< 28 days prior to registration)
* Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only. Both females and males must agree to follow the instructions
* NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Provide written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the study protocol
* Willingness to provide mandatory blood specimens for correlative research
* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

* Active plasma cell leukemia at the time of screening. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, myeloma protein, and skin changes), Waldenstrom Macroglobulinemia
* The only exception is emergency use of a short course of systemic corticosteroids (equivalent to, or less than: dexamethasone 40 mg/day for a maximum of 4 days) before treatment
* Prior belantamab mafodotin therapy. However, patients with prior exposure to another non-belantamab mafodotin anti-BCMA agent such as an anti-BCMA CAR-T or anti-BCMA bispecific antibody will be allowed to participate in the study
* Systemic active infection requiring treatment
* Any unresolved toxicity \>= grade 2 from previous treatment except for alopecia, or peripheral neuropathy up to grade 2
* Any major surgery =\< 4 weeks prior to registration
* Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities except renal impairment) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures
* Evidence of active mucosal or internal bleeding
* Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria
* Participants with previous or concurrent malignancies other than multiple myeloma are excluded, unless the prior malignancy has been considered medically stable for \> 2 years. The participant must not be receiving active therapy, other than hormonal therapy for this disease. NOTE: Participants with curatively treated nonmelanoma skin cancer are allowed without a 2-year restriction.
* Evidence of cardiovascular risk, including any of the following:
* Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities including 2nd degree (Mobitz type II) or 3rd degree atrioventricular (AV) block
* History of myocardial infarction (=\< 6 months), acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 12 weeks of screening
* Class III or IV heart failure as defined by the New York Heart Association functional classification system \[NYHA, 1994\]
* Uncontrolled hypertension
* Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin, or any of the components of the study treatment
* Known human immunodeficiency virus (HIV) infection, unless the participant can meet all of the following criteria:
* Established anti-retroviral therapy (ART) for at \>=4 weeks and HIV viral load \< 400 copies/mL
* CD4+ T-cell (CD4+) counts \>= 350 cells/uL
* No history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections \< 12 months prior
* 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 as relevant
* Patients with hepatitis B will be excluded unless the following criteria can be met:
* If patient's serology shows hepatitis B virus core antibody (HbcAb)+ and hepatitis B surface antigen (HbsAg)-, they must have undetectable hepatitis B virus (HBV) deoxyribonucleic acid (DNA) at screening. Patients will be monitored per protocol. Antiviral treatment would be instituted if HBV DNA becomes detectable
* If patient's serology shows HBsAg+ at screen or within 3 months prior, patients must have undetectable HBV DNA at screening, must have started highly effective antiviral treatment at least 4 weeks prior to registration, and must have baseline imaging per protocol (patients with cirrhosis are excluded). Patients must remain on antiviral treatment throughout the study. Patients will be monitored per protocol
* Note: presence of hepatitis (Hep) B surface antibody (HBsAb) indicating previous vaccination will not exclude a participant.
* Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or =\< 12 weeks prior to first dose of study treatment unless the participant can meet the following criteria:
* RNA test negative
* Successful anti-viral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period \>= 4 weeks
* Current corneal epithelial disease except for mild punctuate keratopathy
* Participant who received plasmapheresis within =\< 7 days prior to registration
* Patients who received prior allogeneic stem cell transplant
* Participant who received a live or live-attenuated vaccine =\< 30 days prior to registration. Ok to receive coronavirus disease (COVID) vaccine at any timepoint during protocol treatment
* Participant is a woman who is pregnant or lactating
* Participant who plans on wearing contact lenses during treatment with belantamab mafodotin

Contacts and Locations

Principal Investigator

Ricardo D. Parrondo, M.D.

PRINCIPAL_INVESTIGATOR

Mayo Clinic

Study Locations (Sites)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980

United States

Collaborators and Investigators

Sponsor: Mayo Clinic

Ricardo D. Parrondo, M.D., PRINCIPAL_INVESTIGATOR, Mayo Clinic

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-04

Study Completion Date2027-05-29

Study Record Updates

Study Start Date2024-01-04

Study Completion Date2027-05-29

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Multiple Myeloma
Refractory Multiple Myeloma