Desensitization in Kidney Transplantation

NCT00908583 | Completed Phase 4 Results

• 1 other identifier: X05295
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 2

Brief Summary

To determine if deletional strategies will provide effective desensitization.

Conditions

HLA Sensitization

Keywords

Alloantibody; Desensitization; Kidney Transplantation; Nephrology; Plasma Cells; Translational Research/Science

Outcome Measures

Primary Outcomes (1)

• Number of Living Donor Transplant Candidates That Are Transplanted

  Number of living donor transplant candidates who convert to a negative flow T- and B-cell crossmatch via desensitization and are subsequently transplanted

  1 year post baseline

Secondary Outcomes (3)

• Overall Safety of Bortezomib

  Study Day 62

• Number of Patients Whose Cytotoxic Panel Reactive Antibody (PRA) is Decreased by 50%

  46 days

• Acute Rejection Rate

  6 months post transplant

Study Arms (5)

Phase 1, two stages

EXPERIMENTAL

Patients will receive 1 dose of rituximab, 4 doses of bortezomib and plasmapheresis. Rituximab will be given at a dose of 375 mg/m2 on day 32. Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds. Bortezomib will be administered on days 1, 4, 8, and 11. For those patients who go on to Stage 2 of desensitization, bortezomib will be administered via IV push over 3-5 seconds during the pre-transplant period on days 32, 35, 39, 42. Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization. With the first and second doses, administer methylprednisolone 100mg via IV push. With the third and fourth doses, administer methylprednisolone 50mg IVP.

Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone

Phase 2, two stages

EXPERIMENTAL

Patients will receive 1 dose of rituximab, 4 doses of bortezomib and plasmapheresis. Rituximab will be given at a dose of 375 mg/m2 on day -7. Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds. Bortezomib will be administered on days 1, 4, 8, and 11. For those patients who go on to Stage 2 of desensitization, bortezomib will be administered via IV push over 3-5 seconds during the pre-transplant period on days 32, 35, 39, 42. Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization. With the first and second doses, administer methylprednisolone 100mg via IV push. With the third and fourth doses, administer methylprednisolone 50mg IVP.

Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone

Phase 3, two stages

EXPERIMENTAL

Patients will receive 1 dose of rituximab and 4 doses of bortezomib. Rituximab will be given at a dose of 375 mg/m2 on day -7. Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds. Bortezomib will be administered on days 1, 4, 8, and 11. For those patients who go on to Stage 2 of desensitization, bortezomib will be administered via IV push over 3-5 seconds during the pre-transplant period on days 23, 26, 30 and 33. Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization. With the first and second doses, administer methylprednisolone 100mg via IV push. With the third and fourth doses, administer methylprednisolone 50mg IVP.

Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone

Phase 4, single stage

EXPERIMENTAL

Patients will receive 1 dose of rituximab and 6 doses of bortezomib. Rituximab will be given at a dose of 375 mg/m2 on day -7. Patients will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds. Bortezomib will be administered during the pre-transplant period on days 1, 4, 8, and 11, 14, and 17. Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization. With the first and second doses, administer methylprednisolone 100mg via IV push. With the third and fourth doses, administer methylprednisolone 50mg IVP.

Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone

Phase 5, single stage

EXPERIMENTAL

Phase 5 evaluated even greater bortezomib dosing density by eliminating the inter-cycle dosing interval. Phase 5 evaluated eight consecutive doses of bortezomib with one dose of rituximab. Rituximab will be given at a dose of 375 mg/m2 on day -7. Patient will receive 1.3 mg/m2 of bortezomib via intravenous push (IVP) over 3-5 seconds. Bortezomib will be administered on days 1, 4, 8, 11, 14, 17, 20, and 23. Methylprednisolone will be administered within 30 minutes of each bortezomib administration in both stages of desensitization. With the first and second doses, administer methylprednisolone 100mg via IV push. With the third and fourth doses, administer methylprednisolone 50mg IVP.

Drug: plasmapheresis; Drug: Bortezomib; Drug: Rituximab; Drug: Methylprednisolone

Interventions

plasmapheresis DRUG

Patients will receive plasmapheresis 1.5 x plasma volume prior to each Bortezomib dose. Plasma volume replacement will be per physician discretion.

Phase 1, two stages; Phase 2, two stages; Phase 3, two stages; Phase 4, single stage; Phase 5, single stage

Bortezomib DRUG

Patients will receive bortezomib as described in protocol

Also known as: Velcade

Phase 1, two stages; Phase 2, two stages; Phase 3, two stages; Phase 4, single stage; Phase 5, single stage

Rituximab DRUG

Patients will receive rituximab as described in protocol

Also known as: Rituxan

Phase 1, two stages; Phase 2, two stages; Phase 3, two stages; Phase 4, single stage; Phase 5, single stage

Methylprednisolone DRUG

Each bortezomib dose will be preceded by intravenous methylprednisolone (100mg for first two doses and 50mg for following doses).

Also known as: Medrol

Phase 1, two stages; Phase 2, two stages; Phase 3, two stages; Phase 4, single stage; Phase 5, single stage

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65
• Voluntary written informed consent
• Patient on deceased donor wait list with a current or peak cytotoxic or calculated panel reactive antibody (PRA) \> 20%

You may not qualify if:

• Myocardial infarction within 6 months
• Patient received investigational drug within 14 days prior to initiation of study treatment
• Serious medical or psychological illness
• Diagnosed with malignancy within three years, except complete research of basal cell carcinoma or squamous cell carcinoma of skin, an insitu malignancy or low risk prostate cancer after curative therapy
• Absolute neutrophil count (ANC) \< 1000
• Receipt of live vaccine within 4 weeks of study entry
• Female subject that is breast feeding

Sponsors & Collaborators

• University of Cincinnati: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (2)

The Christ Hospital

Cincinnati, Ohio, 45267, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

MeSH Terms

Interventions

Plasmapheresis; Bortezomib; Rituximab; Methylprednisolone

Intervention Hierarchy (Ancestors)

Blood Component Removal; Therapeutics; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: E. Steve Woodle
• Organization: University of Cincinnati

woodlees@ucmail.uc.edu

513-558-6001

Study Officials

• E. Steve Woodle, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, FACP

Study Record Dates

• First Submitted: May 26, 2009
• First Posted: May 27, 2009
• Study Start: May 1, 2009
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 1, 2016
• Results First Posted: February 26, 2016

Record last verified: 2016-03

Locations

US (2)