This phase II trial studies how well daratumumab and hyaluronidase-fihj works in treating patients with damage to nerves (polyneuropathy) that is being caused by an immune disorder known as monoclonal gammopathy of undetermined significance (MGUS). MGUS causes an abnormal protein to be found in the blood. This protein is a monoclonal protein or M protein, and is formed within the bone marrow, the soft, blood-producing tissue that fills in the center of most of the bones. The disorder typically does not cause any problems, however in a small proportion of people, the proteins can cause organ problems or nerve problems. Rarely, MGUS can transform into a cancer. Daratumumab is a monoclonal antibody that targets CD-38 (a protein found on the surface of plasma cells) and causes destruction of the abnormal cell, and hyaluronidase, which is a class of protein called endoglycosidase (an enzyme). The hyaluronidase allows daratumumab to be given by an injection under the skin. Daratumumab and hyaluronidase-fihj may be able to stop the bone marrow from making the M protein and causing further damage to nerves.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06046287.
PRIMARY OBJECTIVE:
I. To assess the efficacy of daratumumab and recombinant human hyaluronidase (daratumumab and hyaluronidase-fihj) in MGUS patients, as determined by absolute changes from baseline in functional assessment inflammatory neuropathy cause and treatment (INCAT) sensory (ISS) score.
SECONDARY OBJECTIVES:
I. To assess efficacy by absolute changes in other functional assessments (clinical examination, and nerve conduction velocity studies [NCS]/electromyography [EMG] measures) and by improvement in health-related quality of life measures (the modified Rankin Score, INCAT disability scale, and 36-item Short Form Health Survey [SF-36] score) with treatment of daratumumab and hyaluronidase-fihj.
II. To assess if there is an improvement in MGUS laboratory studies with treatment.
OUTLINE:
Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-2 and on days 1 and 15 of cycles 3-6. Cycles repeat every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo EMG, NCS, and blood sample collection throughout the trial.
After completion of study treatment, patients are followed up at 9 and 12 months.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationMedStar Georgetown University Hospital
Principal InvestigatorKimberley Doucette
