MURINE OKT4A IMMUNOSUPPRESSION IN CADAVER DONOR RENAL-ALLOGRAFT RECIPIENTS - A COOPERATIVE CLINICAL-TRIAL IN A TRANSPLANTATION PILOT-STUDY

Background. A phase I study of anti-CD4 immunosuppression of cadaver d onor rend allograft recipients was conducted by the NIH Cooperative Cl inical Trials in Transplantation to assess safety, tolerability, immun oactivity, and pharmacokinetics of multiple infusions of murine anti-h uman CD4 monoclonal antibody OKT4A. Methods. Thirty patients were enro lled (August 1992 to October 1993) and received OKT4A at dosages of 0. 5 mg/kg (24 patients), 1.0 mg/kg (3 patients), and 2.0 mg/kg (3 patien ts), beginning and continuing for 12 consecutive days with a standard regimen of cyclosporine, azathioprine, and prednisone. OKT4A treatment was continued after surgery if serum creatinine 24 hr after transplan tation was <85% of pretransplantation baseline creatinine. Results. Ni nety-three percent of patients treated at 0.5 mg/kg OKT4A and all pati ents at higher doses had mean peak CD4 saturations in excess of 90%. A human anti-mouse antibody response of >3 times pretreatment levels wa s observed in 84% of patients. There was no evidence of CD4 T cell dep letion. OKT4A was well tolerated without first-dose side effects. For the 19 eligible patients treated with 0.5 mg/kg OKT4A with initial gra ft function, the 3-month treated rejection rate was 37%. The 2-year gr aft survival rate for all 30 patients enrolled was 83%, and for the 19 eligible patients, 95%. Conclusions. The high percentage of CD4 satur ation, the minimal side effects, the observation of a low 3-month reje ction rate, and an excellent 2-year graft survival rate in patients tr eated with 0.5 mg/kg OKT4A support the continued investigation of an a nti-CD4 approach to immunosuppressive therapy.