Kidney TransplantationPhase 4NCT00782821
Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients
A Phase 4 study testing Rabbit Antithymocyte Globulin, Velcade and Rituxan in people with Kidney Transplantation, run by University of Cincinnati at 2 sites in United States.
Trial summary
The purpose of this research study is to find out the effects of adding B lymphocyte modulating agents in patients at risk for rejection receiving an anti-rejection (immunosuppressive) regimen of Thymoglobulin® induction with Prograf®, Cellcept® and corticosteroid therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Rabbit Antithymocyte Globulin, Velcade and Rituxan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2008to Mar 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Patient is between the 18 and 65 years of age, inclusive.
- Patient is considered high risk for acute rejection based on any one of the following:
- Patient has a current Cytotoxic PRA≥ 20% or a peak Cytotoxic PRA ≥50%
- Patient has a T or B-cell positive crossmatch (by flow cytometry) with confirmed donor-specific antibodies on solid-phase assay.
Show all 11Show fewer
- Historical positive serologic or cytotoxic crossmatch or DSA to donor
- Prior allograft loss with a history of more than one acute rejection episode.
- Female subject is either postmenopausal for at least 1 year prior to initiation of study treatment, is surgically sterilized, or if of childbearing potential, agrees to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agrees to completely abstain from heterosexual intercourse. Women of childbearing potential must have a negative serum pregnancy test within the last 48 hours prior to receiving study medication.
- Male subjects, even if surgically sterilized (i.e. status post-vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
- Patient must have no known contraindications to treatment with bortezomib, rituximab, or thymoglobulin.
Who cannot join
- Patients that have previously received or are receiving an organ transplant other than kidney.
- Patient who lost a previous allograft due to recurrence of disease
- Patient is receiving a HLA identical living related kidney transplant
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal or polyclonal antibodies
- Patients with an absolute neutrophil count of < 1,000/mm3 or platelet count < 100,000/mm3within 30 days of consent.
- Patient has Grade 2 peripheral neuropathy by CTCAE criteria within 14 days before enrollment.
Show all 16Show fewer
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 9.3), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any abnormality on ECG performed within 30 days of consent has to be documented by the investigator or the patient's transplant nephrologist as not medically relevant.
- Patients who are anti-HIV-positive, or HBsAg-positive or Anti-HCV positive on testing performed within one year of consent.
- Diagnosed or treated for malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
- Patients with current or recent severe systemic infections within the 2 weeks prior to initiation of study treatment.
- Receipt of a live vaccine within 4 weeks prior to initiation of study treatment.
- Use of other investigational drugs within 30 days or 5 half-lives prior to initiation of study treatment, whichever is longer
- Evidence of severe liver disease by medical history or physical exam with abnormal liver profile (aspartate aminotransferase [AST], alanine aminotransferase [ALT] or total bilirubin > 1.5 times upper limit of normal [ULN]) on testing performed within 30 days of consent.
- Pregnant or nursing (lactating) women and women who might become pregnant during the study. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum -human chorionic gonadotropin pregnancy test result within the last 48 hours prior to receiving study medication. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- EBV serologic mismatch (i.e. EBV+ donor transplanted to EBV- recipient)
- CMV serologic mismatch (i.e. CMV+ donor transplanted to CMV- recipient)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Christ Hospital
Cincinnati, Ohio, 45202
The University Hospital
Cincinnati, Ohio, 45219
About this study
Official title: Targeted Therapy for High Immunologic Risk Renal Transplant Recipients: A Prospective, Randomized, Open-Label Pilot Study of B-Cell Depleting Therapy in Combination With Anti-Thymocyte Globulin [Rabbit] (Thymoglobulin®, Genzyme), Tacrolimus (Prograf®, Astellas), Mycophenolate Mofetil (CellCept®, Roche) and Corticosteroid Minimization
The purpose of this research study is to find out the effects of adding B lymphocyte modulating agents in patients at risk for rejection receiving an anti-rejection (immunosuppressive) regimen of Thymoglobulin® induction with Prograf®, Cellcept® and corticosteroid therapy.
Read the detailed description
Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATGþrituximab, rATGþbortezomib or rATGþrituximabþbortezomib.
- Conditions
- Kidney Transplantation
- Being tested
- Rabbit Antithymocyte Globulin, Velcade, Rituxan
- Keywords
- Kidney, Renal, Rejection, High risk, Induction, Immunology, Transplantation, B Cell, Allograft, Desensitization
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rabbit Antithymocyte GlobulinDrug
Also called Thymoglobulin, rATG
rATG will be given 1.5mg/kg intravenous (IV) per dose.
VelcadeDrug
Also called bortezomib
Velcade will be given 1.3mg/m2 via intravenous push (IVP) per dose.
RituxanDrug
Also called Rituximab
Given via IV per group assignment.
| Study group | Role | What they receive |
|---|---|---|
| Rabbit Antithymocyte Globulin (rATG) | Active comparator | Rabbit Antithymocyte Globulin (rATG) 1.5mg/kg per dose x 6 doses rATG was administered on post-op day 0, 2, 4, 6, 8 and 10. Receives: Drug: Rabbit Antithymocyte Globulin |
| RATG/Rituxan | Experimental | Rabbit Antithymocyte Globulin (rATG)/Rituxan 1.5mg/kg per dose x 5 doses of rATG. 375mg/m2 x 1 dose of rituxan. rATG was administered on post-op day 0, 2, 4, 6 and 8. Rituxan was given on post-op day 1. Receives: Drug: Rabbit Antithymocyte Globulin; Drug: Rituxan |
| RATG/Velcade | Experimental | Rabbit Antithymocyte Globulin (rATG) /Velcade 1.5mg/kg per dose x 5 doses of rATG. 1.3mg/m2 per dose x 4 doses of velcade. rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. Receives: Drug: Rabbit Antithymocyte Globulin; Drug: Velcade |
| RATG/Rituxan/Velcade | Experimental | Rabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade 1.5mg/kg per dose x 4 doses of rATG. 200mg/m2 for 1 dose of rituxan. 1.3mg/m2 per dose x 4 doses of velcade.
rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. Rituxan was given on post-op day 1. Receives: Drug: Rabbit Antithymocyte Globulin; Drug: Velcade; Drug: Rituxan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection
Antibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria.
Acute rejection IA - cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/tubular cross section or group of 10 tubular cells).
IB - cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of severe tubulitis (>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising >25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
Measured: 6 months
Secondary outcomes (4)
Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
Antibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria. Rejection due, at least in part, to documented anti-donor antibody ('suspicious for' if antibody not demonstrated); may coincide with categories 3, 4 and 5.
Grade I. ATN-like - C4d+, minimal inflammation Grade II. Capillary- margination and/or thromboses, C4d+ Grade III. Arterial - v3, C4d+
Measured: 6 months
Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
Acute cellular rejection IA - cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/tubular cross section or group of 10 tubular cells).
IB - cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of severe tubulitis (>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising >25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
Measured: 6 months
Patient Survival at 12 Months
Patient was still alive 12 months post study enrollment.
Measured: 12 months
Patient Allograft Survival at 12 Months
Patient's allograft was still functioning at 12 months post study enrollment
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2008 (estimated)
- Study startSep 2008
- Primary completionFeb 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Genzyme, a Sanofi Company
- Responsible party
- Principal investigator, E. Steve Woodle, University of Cincinnati
- Investigators
- E. Steve Woodle, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00782821
- Sponsor's protocol ID
- X05274
- Status last verified
- Dec 2015
- First submitted
- 29 Oct 2008
- Last updated
- 20 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Therapy for High Immunologic Risk Renal Transplant Recipients: A Prospective, Randomized, Open-Label Pilot Study of B-Cell Depleting Therapy in Combination With Anti-Thymocyte Globulin [Rabbit] (Thymoglobulin®, Genzyme), Tacrolimus (Prograf®, Astellas), Mycophenolate Mofetil (CellCept®, Roche) and Corticosteroid Minimization
- ClinicalTrials.gov ID
- NCT00782821
- Acronym / sponsor ID
- X05274
- Conditions
- Kidney Transplantation
- Keywords
- Kidney, Renal, Rejection, High risk, Induction, Immunology, Transplantation, B Cell
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Genzyme, a Sanofi Company
- Study start
- Sep 2008
- Primary completion
- Feb 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 31 Oct 2008 (estimated)
- Results
- Posted 20 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to find out the effects of adding B lymphocyte modulating agents in patients at risk for rejection receiving an anti-rejection (immunosuppressive) regimen of Thymoglobulin® induction with Prograf®, Cellcept® and corticosteroid therapy.
Detailed description
Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATGþrituximab, rATGþbortezomib or rATGþrituximabþbortezomib.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Rabbit Antithymocyte Globulin (rATG) | Active comparator | Drug: Rabbit Antithymocyte GlobulinRabbit Antithymocyte Globulin (rATG) 1.5mg/kg per dose x 6 doses rATG was administered on post-op day 0, 2, 4, 6, 8 and 10. |
| RATG/Rituxan | Experimental | Drug: Rabbit Antithymocyte Globulin, Drug: RituxanRabbit Antithymocyte Globulin (rATG)/Rituxan 1.5mg/kg per dose x 5 doses of rATG. 375mg/m2 x 1 dose of rituxan. rATG was administered on post-op day 0, 2, 4, 6 and 8. Rituxan was given on post-op day 1. |
| RATG/Velcade | Experimental | Drug: Rabbit Antithymocyte Globulin, Drug: VelcadeRabbit Antithymocyte Globulin (rATG) /Velcade 1.5mg/kg per dose x 5 doses of rATG. 1.3mg/m2 per dose x 4 doses of velcade. rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. |
| RATG/Rituxan/Velcade | Experimental | Drug: Rabbit Antithymocyte Globulin, Drug: Velcade, Drug: RituxanRabbit Antithymocyte Globulin (RATG) / Rituxan / Velcade 1.5mg/kg per dose x 4 doses of rATG. 200mg/m2 for 1 dose of rituxan. 1.3mg/m2 per dose x 4 doses of velcade. rATG was administered on post-op day 0, 2, 4, and 6. Velcade was administered on post-op day 0, 3, 7 and 10. Rituxan was given on post-op day 1. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Each patient must meet all of the following inclusion criteria to be enrolled in the study:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Patient is between the 18 and 65 years of age, inclusive.
- Patient is considered high risk for acute rejection based on any one of the following:
- Female subject is either postmenopausal for at least 1 year prior to initiation of study treatment, is surgically sterilized, or if of childbearing potential, agrees to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agrees to completely abstain from heterosexual intercourse. Women of childbearing potential must have a negative serum pregnancy test within the last 48 hours prior to receiving study medication.
Key exclusion criteria (16 listed)
- Patients that have previously received or are receiving an organ transplant other than kidney.
- Patient who lost a previous allograft due to recurrence of disease
- Patient is receiving a HLA identical living related kidney transplant
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal or polyclonal antibodies
- Patients with an absolute neutrophil count of < 1,000/mm3 or platelet count < 100,000/mm3within 30 days of consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rabbit Antithymocyte GlobulinAlso: Thymoglobulin, rATGrATG will be given 1.5mg/kg intravenous (IV) per dose. | Drug | RATG/Rituxan, RATG/Rituxan/Velcade, RATG/Velcade, Rabbit Antithymocyte Globulin (rATG) |
| VelcadeAlso: bortezomibVelcade will be given 1.3mg/m2 via intravenous push (IVP) per dose. | Drug | RATG/Rituxan/Velcade, RATG/Velcade |
| RituxanAlso: RituximabGiven via IV per group assignment. | Drug | RATG/Rituxan, RATG/Rituxan/Velcade |
Primary outcome
Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection
Time frame: 6 months
Antibody mediated rejection demonstrated to be due to, atleast in part, to anti-donor antibody at 6 months by Banff 97' criteria. Acute rejection IA - cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of moderate tubulitis (>4 mononuclear cells/tubular cross section or group of 10 tubular cells). IB - cases with significant interstitial infiltration (>25% of parenchyma affected) and foci of severe tubulitis (>10 mononuclear cells/tubular cross section or group of 10 tubular cells) IIA - cases with mild to moderate intimal arteritis (v1) IIB - cases with server intimal arteritis comprising >25% of the luminal area (v2) III - case with transmural arteritis and/or arterial fibrinoid change and necrosis of medical smooth muscle cells (v3 with accompanying lymphoctic inflammation)
4 secondary outcomes
Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
Time frame: 6 months
Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
Time frame: 6 months
Patient Survival at 12 Months
Time frame: 12 months
Patient Allograft Survival at 12 Months
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
E. Steve Woodle, MD principal investigator
University of Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Rabbit Antithymocyte Globulin, Velcade and Rituxan in people with Kidney Transplantation, run by University of Cincinnati at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2016.