This phase I trial studies the side effects of daratumumab and hyaluronidase-fihj when given before standard of care (SOC) desensitization, and to see how well it works in lowering donor-specific antibodies (DSA) in patients undergoing a donor bone marrow or peripheral blood stem cell transplantation. In a donor stem cell transplantation, stem cells that come from the bone marrow or peripheral blood of a donor are transplanted into the patient. Plasma cells are white blood cells that are important in the immune system. Plasma cells produce antibodies that fight infections. High levels of DSA mean plasma cells are producing antibodies that will attack and potentially destroy the donor's blood cells. Daratumumab and hyaluronidase-fihj is a monoclonal antibody that targets plasma cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving daratumumab and hyaluronidase-fihj before SOC desensitization may be safe, tolerable, and/or effective in lowering DSA in patients undergoing a donor bone marrow or peripheral blood stem cell transplantation.
Additional locations may be listed on ClinicalTrials.gov for NCT06398457.
Locations matching your search criteria
United States
Maryland
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer CenterStatus: Active
Contact: Christian Burris Gocke
Phone: 443-287-7104
PRIMARY OBJECTIVES:
I. To evaluate the ability of the addition of daratumumab prior to standard desensitization therapy to reduce DSA levels to low enough levels for proceeding to start the allogeneic bone marrow transplantation (alloBMT) preparative regimen.
II. The safety of this regimen where the proportion of patients with grade 3 or higher toxicities attributable to daratumumab for one cycle of daratumumab and recombinant human hyaluronidase (Darzalex Faspro [daratumumab and hyaluronidase-fihj]) will be calculated.
SECONDARY OBJECTIVES:
I. Time to neutrophilic and platelet recovery.
II. T-cell chimerism by day +60.
III. Primary graft failure rate.
OUTLINE:
Patients receive daratumumab and hyaluronidase-fihj subcutaneously (SC) over 3-5 minutes on days -43, -36, -29, and -22 in the absence of disease progression or unacceptable toxicity. Patients also undergo serum sample collection and Johns Hopkins-Donor Specific Antibody (JH-DSA) response evaluation prior to receiving each dose of daratumumab and hyaluronidase-fihj.
Patients then undergo standard of care (SOC) desensitization with therapeutic plasma exchange (TPE), intravenous immunoglobulin therapy (IVIG), tacrolimus, and mycophenolate mofetil (MMF) between days -15 and -7 in the absence of disease progression or unacceptable toxicity. Patients also undergo serum sample collection and JH-DSA response evaluation on days -15 and -8.
Patients with DSA strength of II or less and at least a 10% decrease in mean fluorescence intensity (MFI) from the baseline value continue to receive SOC desensitization with TPE, IVIG, tacrolimus, and MMF from days -6 to -1.
Patients also begin SOC transplant preparative regimen with fludarabine, cyclophosphamide, and total-body irradiation from days -6 to -1 or days -6 to 0.
Patients undergo serum sample collection and JH-DSA response evaluation followed by a single SOC desensitization with TPE and IVIG on day -1.
Patients then undergo SOC alloBMT or peripheral blood stem cell transplantation on day 0.
Patients may receive additional SOC desensitization with TPE and IVIG on days +1 and +2 based on day -1 JH-DSA response evaluation.
Patients also undergo serum sample collection and JH-DSA response evaluation on days +3, +5, +14, +21, and +28.
After completion of study treatment, patients are followed up to day +60.
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorChristian Burris Gocke
