Rituximab Therapy for Patients on Kidney Transplant Waiting List With Positive Donor Specific Crossmatch to Living Donor

• Status: Completed
• Trial end date: 2007-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objectives:

• Conversion of a positive donor specific cross-match to a living donor to a negative cross-match thereby allowing successful renal transplantation.

• Transplant success or failure following the desensitization protocol.

• Determination of the effect of rituximab on the kinetics of donor specific antibodies (DSA).

• Determination of the effect of rituximab on the kinetics of B-cell subpopulations in peripheral blood and/or secondary lymphoid organs (lymph node biopsies at time of transplant, if available) in both responders and non-responders using flow cytometry and/or immunohistochemistry.

Secondary Objectives:

-Decrease in incidence of humoral rejection to less than 50 % at 1 year.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborators: Biogen; Genentech, Inc.
• Treatments: Rituximab

Criteria

Inclusion Criteria:

• Active status on a kidney transplant waiting list for over 2 years

• Donor specific antibody titer <= 1:128 (Class I, Class II or both) by cytotoxicity

• Signed and dated informed consent

• Age ≥ 18 years

• Positive cross-match against a living donor

Exclusion Criteria:

• Donor specific antibody titer greater than 1:128 (Class I, Class II or both) by cytotoxicity

• Inactive status on a kidney transplant list

• Treatment with any investigational agent within 4 weeks of screening or 5-half-lives of the investigational drug (whichever is longer)

• Receipt of a live vaccine within 4 weeks prior to randomization

• Previous Treatment with Rituximab (MabThera/Rituxan)

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies

• Positive history of HIV

• Positive history of Hepatitis B and/or Hepatitis C

• History of recurrent significant infection or history of recurrent bacterial infections

• Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening

• History of drug, alcohol, or chemical abuse within 6 months prior to screening

• Pregnancy (a negative serum or urine pregnancy test should be performed for all women of childbearing potential within 7 days of treatment)

• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment

• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

• History of psychiatric disorder

• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)

• Laboratory Exclusion Criteria (at Screening)

• Hemoglobin: < 7g/dL

• Platelets: <100,000/mm3

• AST or ALT >2X Upper limit of normal

• Known history of positive Hepatitis B or C serology

• Immunization status to be confirmed per transplant protocol. Review of the subject's immunization status for the following vaccinations will be ascertained: tetanus; diptheria; influenza; pneumococcal polysaccharide; Varicella; measles, mumps and rubella (MMR); and hepatitis B. Subjects who are considered to be at high risk for hepatitis B virus (HBV) infection and for whom the investigator has determined that immunization is indicated should complete the entire HBV vaccine series (per routine dialysis protocol) at least 4 weeks prior to participation in the study.

Immunization with a live vaccine is specifically excluded during the study.