Daratumumab and Belatacept for Desensitization

Conditions

• Highly Sensitized Prospective Kidney Transplant Recipients

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Not accepted

Interventions

• daratumumab — BIOLOGICAL
  Daratumumab is a CD38 (Cluster of Differentiation 38)-directed cytolytic monoclonal antibody indicated for the treatment of multiple myeloma. In this study, daratumumab will be used in highly sensitized subjects without myeloma who are awaiting a kidney transplant. Definition of highly sensitized: Potential kidney transplant recipients with either: * calculated panel reactive antibodies (cPRA) ≥99.9% awaiting deceased donor transplant, or * cPRA \>98% (with \>5 years of waiting time) awaiting living donor transplant
• belatacept — BIOLOGICAL
  Belatacept, a monoclonal antibody, is indicated for the prophylaxis of organ rejection in adult patients receiving a kidney transplant. In this study, belatacept will be used in subjects who have not received a kidney transplant.
• Bone marrow aspiration — PROCEDURE
  Subjects will undergo a bone marrow aspiration prior to starting the study regimen and at 12 weeks after starting the study regimen. In subjects who undergo a kidney transplant during the study, another bone marrow aspiration will be done if it has been \>4 weeks since the previous bone marrow aspiration.

Study Details

Some kidney transplant candidates have a very low chance of getting a kidney transplant because their immune systems are "highly sensitized" to most kidney donors. Being "highly sensitized" means that they will likely have to wait a long time (more than 5 years) before an acceptable donor is found for them or, they never receive a compatible donor, and die on waitlist. The purpose of this study is to find out whether two drugs, daratumumab (Darzalex®), and belatacept (Nulojix®), can make these kidney transplant candidates less sensitized, and make it easier and quicker to find a kidney donor for them.

Key Dates

Start date

Nov 1, 2021

Status verified

Jan 2026

Primary completion

Mar 31, 2027

Completion

Apr 30, 2028

Study Design

Enrollment

19 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1 (N=5 Subjects)
  Multiple intravenous infusions of daratumumab and belatacept over 10 weeks: * Daratumumab will be administered intravenously at a dose of 8 mg/kg weekly for 4 weeks, then every other week for 4 weeks (week 9 and week 11). The dose administered will be calculated based on the actual body weight of the subject at each visit. * Belatacept will be administered intravenously at a dose of 10 mg/kg every 2 weeks starting at week 8 (dosed at weeks 8, 10, 12, and 14). The total infusion dose of belatacept will be based on the actual body weight of the subject at the baseline visit, and will not be modified during the course of therapy, unless there is a change in body weight of greater than 10%.
• Experimental: Cohort 2 (N=10 Subjects)
  The enrollment of ten additional subjects is dependent on the results in Cohort 1. Multiple intravenous infusions of daratumumab and belatacept over 14 weeks:° * Daratumumab will be administered intravenously at a dose of 8 mg/kg for the first dose, then 16 mg/kg for subsequent given weekly for 3 weeks, then every 2 weeks for 2 doses (week 9 and week 11). The dose administered will be calculated based on the actual body weight of the subject at each visit. * Belatacept will be administered intravenously at a dose of 10 mg/kg every 2 weeks starting at week 8 (dosed at weeks 8, 10, 12, 14, 16 and 18). The total infusion dose of belatacept will be based on the actual body weight of the subject at the baseline visit and will not be modified during the course of therapy, unless there is a change in body weight of greater than 10%. * Was modified based on the safety and efficacy analysis of Cohort 1.

Primary Outcome Measure

Proportion of subjects who have not met a subject stopping rule and remain free of all of the safety events listed in the outcome description, through 26 weeks after starting treatment or until receiving a transplant, whichever occurs earlier [ Time Frame: Baseline up to 26 weeks post treatment initiation ]

Locations (1)

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