A Safety Study of Tocilizumab to Improve Transplant Rates in Highly Sensitized Patients Awaiting Kidney Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Stanley Jordan, MD, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT01594424
First received: May 4, 2012
Last updated: February 17, 2014
Last verified: February 2014
  Purpose

In this Phase I/II trial, 10 highly sensitized patients will be entered after informed consent and will receive Intravenous Immunoglobulin (IVIG) at 2 gm/kg + Tocilizumab 8 mg/kg x 5 doses on days 15, 45, 75, 105, 119, 135, and 149. If robust reductions in anti-HLA antibody are seen, patients will progress to kidney transplantation when an "acceptable" crossmatch is achieved with a living donor (LD) or deceased donor (DD). Those receiving transplants will also receive Tocilizumab infusion monthly X7 doses post-transplant. All subjects will have intensive monitoring of Donor Specific Antibodies (DSA), viral PCRs, and routine post-transplant labs. At 6 months post-transplant, those who have retained their transplanted kidney will have a protocol biopsy.


Condition Intervention Phase
End Stage Renal Disease (ESRD)
Drug: Tocilizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Tocilizumab + Intravenous Immunoglobulin (IVIG) as Agents to Reduce Donor-Specific Anti-HLA Antibodies (DSA) and Improve Transplant Rates in Highly-HLA Sensitized Patients Awaiting Kidney Transplantation

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • serious infectious complications [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    patients will be in the study for up to 2 years


Estimated Enrollment: 10
Study Start Date: June 2012
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IVIG + Tocilizumab Drug: Tocilizumab
Tocilizumab 8mg/kg on Days 0, 15, 30, 45, 75, 105, 119, 135, 149, and 180
Other Name: Actemra®

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • End-stage renal disease.
  • No known contraindications for therapy with IVIG 10%/Actemra®.
  • Age 18-65 years at the time of screening.
  • CPRA > 50% demonstrated on 3 consecutive samples, UNOS wait time sufficient to allow DD offers, history of sensitizing events, positive crossmatch with the intended donor. LDs with DSA and Crossmatch positivity.
  • Subject/Parent/Guardian must be able to understand and provide informed consent.

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
  • Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening.
  • Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti¬CD3, anti-CD19 and anti-CD20 within 6 months of baseline.
  • Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline
  • Immunization with a live/attenuated vaccine within 2 months prior to baseline.
  • Previous treatment with TCZ (an exception to this criterion may be granted for single dose exposure upon application to the sponsor on a case-by-case basis).
  • Any previous treatment with alkylating agents such as chlorambucil, (within 1 year) or with total lymphoid irradiation.

Exclusions for General Safety:

  • History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
  • Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease (including complicated diverticulitis, ulcerative colitis, or Crohn's disease.)
  • Current liver disease as determined by principal investigator unless related to primary disease under investigation
  • Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds). These are limited to non-access related infections.
  • 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.
  • Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patients treated for tuberculosis with no recurrence in 3 years are permitted.
  • Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
  • Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised and cured), or breast cancer diagnosed within the previous 20 years unless related to primary disease under investigation.
  • Pregnant women or nursing (breast feeding) mothers.
  • Patients with reproductive potential not willing to use an effective method of contraception.
  • History of alcohol, drug or chemical abuse within 1 year prior to screening.
  • Neuropathies or other conditions that might interfere with pain evaluation unless related to primary disease under investigation.
  • Patients with lack of peripheral venous access.
  • Body weight of > 150 kg.

Laboratory Exclusion criteria (at screening):

  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN)
  • Total Bilirubin > ULN
  • Platelet count < 100 x 109/L (100,000/mm3)
  • Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)
  • White Blood Cells < 3.0 x 109/L (3000/mm3)
  • Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)
  • Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)
  • Positive Hepatitis BsAg, or Hepatitis C antibody
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01594424

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Investigators
Principal Investigator: Stanley Jordan, MD Cedars-Sinai Medical Center
  More Information

No publications provided

Responsible Party: Stanley Jordan, MD, Medical Director, Medical Director, Renal Transplantation & Transplant Immunotherpay, Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier: NCT01594424     History of Changes
Other Study ID Numbers: Actemra + IVIG
Study First Received: May 4, 2012
Last Updated: February 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Cedars-Sinai Medical Center:
Donor-Specific Anti-HLA Antibodies
Kidney Transplantation

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014