Rituximab Treatment to Block HLA Antibodies in Renal Transplant Recipients

NCT00261547 | Withdrawn Phase 1 DMC

• 1 other identifier: 2005p001524
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine if administration of rituximab blocks the development of donor specific antibodies (DSA) in transplant recipients who have developed renal dysfunction and DSA after renal transplant. It is hoped that by blocking DSA production renal function will stabilize or improve.

Conditions

Chronic Rejection; Kidney Insufficiency

Keywords

Kidney transplantation; HLA

Outcome Measures

Primary Outcomes (2)

• Negative DSA by Luminex beads or ELISA

  at 12 months post study medication

• Lack of C4d deposition in peritubular capillary

  on 12 month renal biopsy

Secondary Outcomes (2)

• Renal allograft function: Serum creatinine, Calculated creatinine clearance, Urine protein, Urine protein-creatinine ratio

  12 months after study entry compared to the baseline

• Change in chronic rejection pathology indices

  on 12-month renal biopsy compared to baseline biopsy.

Study Arms (1)

Rituximab

EXPERIMENTAL

this study has only one arm as the treatment group

Drug: Rituximab

Interventions

Rituximab DRUG

All subjects will be treated with Rituximab 1000 mg (1 g) intravenously on days 1 and 15.

Also known as: Rituxan

Rituximab

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Recipient of a primary cadaver or living donor renal allograft
• years of age
• At least 6 months and no more than 10 years post renal transplant
• Serum clearly positive for defined DSA
• Renal biopsy positive for C4d staining within 28 days before study Day 1 treatment
• Blood positive for Cd 19/20 cells at greater than/equal to 50 % of lower limit of normal
• Baseline serum creatinine 1.7-3.0 mg/dl
• On stable doses of tacrolimus and MMF for at least 1 month prior to study entry
• Able and willing to sign IRB approved consent form and comply with the requirements of the screen, treatment and follow-up phase of the protocol
• Negative serum pregnancy test (women of child bearing potential)
• Men and women of reproductive potential agree to use an acceptable method of birth control during treatment, for twelve months after treatment completion, or until B cell counts return to normal, whichever is longer

You may not qualify if:

• Hemoglobin: \< 8.5 gm/dL
• Platelets: \< 100.00/mm
• White blood cell count: \< 3000/mm3
• AST or ALT . 2.5 x Upper Limit of Normal unless related to primary disease
• Positive Hepatitis B or C serology
• History of positive HIV
• Treatment with any investigational agen 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 study entry
• Previous treatment with rituximab (rituxan)
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of recurrent infections
• Known active bacterial, viral, fungal, mycobacterial or other infection or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• Ongoing use of high dose steroids (\>10mg/day) or unstable steroid dose in the past 4 weeks.
• Lack of peripheral venous access
• History of drug, alcohol or chemical abuse within 6 months prior to screen

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nina Tolkoff-Rubin, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: December 1, 2005
• First Posted: December 5, 2005
• Study Start: December 1, 2005
• Primary Completion: November 1, 2007
• Study Completion: November 1, 2007
• Last Updated: October 23, 2023

Record last verified: 2023-10