Belantamab Mafodotin, Lenalidomide, and Daratumumab for the Treatment of Relapsed, Refractory, or Previously Untreated Multiple Myeloma

NCT04892264 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: MC1989NCI-2021-0347920-009533
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose and effect of belantamab mafodotin given together with lenalidomide and daratumumab in treating patients with multiple myeloma that has come back (relapsed), does not respond to treatment (refractory) or for which the patient has not received treatment in the past (previously untreated). Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called 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. Lenalidomide is an immunomodulatory drug (altering the immune effects on the tumor cell). Daratumumab is a drug that is a monoclonal antibody that is directed towards a protein on the myeloma cell. Giving belantamab mafodotin together with lenalidomide and daratumumab may kill more cancer cells.

Conditions

Plasma Cell Myeloma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of belantamab in combination with daratumumab and lenalidomide in patients with relapsed and/or refractory multiple myeloma (Phase I)

  The MTD will be determined by the dose limiting toxicities (DLTs) seen in cycle 1 of the therapy in the phase I portion. The phase II portion will be based on the determined MTD. MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients).

  Up to 28 days

• Complete response rate with belantamab, daratumumab, and lenalidomide, OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone, when used as initial therapy (Phase II)

  A confirmed response is defined as a patient who has achieved a stringent complete response (sCR) or CR (as defined by the International Myeloma Working Group criteria) and maintained it on two consecutive evaluations at least 2 weeks apart.

  After completion of induction therapy

Secondary Outcomes (6)

• Incidence of toxicity (Phase I)

  Up to 3 years

• Overall response rate

  Up to 3 years

• Greater than or equal to very good partial response (VGPR) rate

  Up to 3 years

• Progression-free survival

  From registration to the earliest date of documentation of disease progression or relapse or death due to any cause, assessed up to 3 years

• Time to response

  Time between the date of first dose and the first documented evidence of a partial response or better, assessed up to 3 years

Study Arms (2)

Arm A (belantamab mafodotin, lenalidomide, daratumumab)

EXPERIMENTAL

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles (starting cycle 13), lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Belantamab Mafodotin; Biological: Daratumumab; Drug: Lenalidomide; Other: Quality-of-Life Assessment; Procedure: Biospecimen Collection; Procedure: Skeletal Survey X-Ray; Procedure: Low Dose Computed Tomography of the Whole Body; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy

Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

EXPERIMENTAL

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of cycles 2, 4, 6, 8, 10, and 12, lenalidomide PO QD on days 1-21, daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 3, and days 1 and 15 on cycles 5, 7, 9, and 11. Patients also receive dexamethasone PO on days 1, 8, 15 and 22. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of even numbered cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1 of odd numbered cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Belantamab Mafodotin; Biological: Daratumumab; Drug: Dexamethasone; Drug: Lenalidomide; Other: Quality-of-Life Assessment; Procedure: Biospecimen Collection; Procedure: Skeletal Survey X-Ray; Procedure: Low Dose Computed Tomography of the Whole Body; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy

Interventions

Belantamab Mafodotin BIOLOGICAL

Given IV

Also known as: Belantamab Mafodotin-blmf, Blenrep, GSK2857916, J6M0-mcMMAF

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Daratumumab BIOLOGICAL

Given IV

Also known as: Darzalex, HuMax-CD38, JNJ-54767414

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Skeletal Survey X-Ray PROCEDURE

Undergo X-ray skeletal survey

Also known as: Skeletal Survey

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Low Dose Computed Tomography of the Whole Body PROCEDURE

Undergo whole body low dose CT

Also known as: Low-dose Whole-body CT, Whole Body Low Dose Computed Tomography, Whole Body Low Dose CT, Whole-body Low-dose CT

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm A (belantamab mafodotin, lenalidomide, daratumumab); Arm B (belantamab mafodotin, lenalidomide, daratumumab, Dxevo)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Phase I: Relapsed or refractory multiple myeloma with at least one prior line of therapy that includes a proteasome inhibitor and an immunomodulatory drug. Patient should be refractory to lenalidomide
• Phase II: Previously untreated multiple myeloma (diagnosed by International Myeloma Working Group \[IMWG\] criteria) or have received no more than one cycle of Standard of Care treatment regimen
• Note: Prior radiation therapy for the treatment of solitary plasmacytoma is permitted. Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted. Any additional agents not listed must be approved by the principal investigator
• Measurable disease
• Note: Phase I patients can enter trial with M spike \>= 0.5 g/dl
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1200/mm\^3 (obtained =\< 14 days prior to registration)
• Platelet count \>= 100,000/mm\^3 (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver involvement) (obtained =\< 14 days prior to registration)
• Prothrombin time (PT)/International Normalized Ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained =\< 14 days prior to registration)
• Calculated creatinine clearance \>= 30 ml/min using the Cockcroft-Gault formula (obtained =\< 14 days prior to registration)
• Female participants: Female participant is eligible to participate if she is not pregnant or breast feeding, and at least one of the following conditions applies:

You may not qualify if:

• Monoclonal gammopathy of undetermined significance or smoldering multiple myeloma
• Major surgery =\< 28 days prior to registration
• Plasmapheresis =\< 14 days prior to registration
• Diagnosed or treated for another malignancy =\< 2 years prior to registration or previously diagnosed with another malignancy and have any evidence of residual disease
• Note: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (hormone therapy, chemotherapy, or immunotherapy) for their cancer
• Receiving any other concurrent chemotherapy, systemic steroids, any ancillary therapy considered investigational for treatment of multiple myeloma, or receiving radiotherapy =\< 14 days or five half-lives, whichever is shorter, prior to first dose of study treatment. Note: Bisphosphonates are considered to be supportive care rather than therapy and are thus allowed while on protocol treatment
• Known to be human immunodeficiency virus (HIV) positive
• Presence of positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment
• Note: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained
• Note: Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing
• Uncontrolled intercurrent illness including, but not limited to:
• Ongoing or active infection (defined as infection undergoing treatment)
• Active mucosal or internal bleeding
• Social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Lenalidomide; Specimen Handling; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Shaji K. Kumar, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 19, 2021
• Study Start: June 3, 2021
• Primary Completion: March 18, 2024
• Study Completion: March 18, 2024
• Last Updated: May 18, 2025

Record last verified: 2025-05

Locations

US (1)