CompletedNCT00782821Updated Jan 20, 2016Results posted

Randomized Trial of Induction Therapies in High Immunological Risk Kidney Transplant Recipients

A Phase 4 interventional study of Rabbit Antithymocyte Globulin and Velcade in Kidney Transplantation, sponsored by University of Cincinnati. Completed at 2 sites in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2016-01-20.

Sponsored by University of Cincinnati · Phase 4, Interventional, and Prevention

Phase: Phase 4
Study type: Interventional
Enrollment: 40
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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 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 studied

Kidney Transplantation

Keywords

Kidney
Renal
Rejection
High risk
Induction
Immunology
Transplantation
B Cell
Allograft
Desensitization

In context

Lead sponsor

University of Cincinnati is the lead sponsor of 314 studies on the registry; 43 are open to participants now.

Of its 22 completed or terminated interventional studies of FDA-regulated products, 15 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.
- 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.

Exclusion criteria

Exclusion Criteria

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.
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)

Study design

Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 40 participants (actual)

Study arms

Active comparator
Rabbit Antithymocyte Globulin (rATG)
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.
Drug: Rabbit Antithymocyte Globulin
Experimental
RATG/Rituxan
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.
Drug: Rabbit Antithymocyte Globulin · Drug: Rituxan
Experimental
RATG/Velcade
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.
Drug: Rabbit Antithymocyte Globulin · Drug: Velcade
Experimental
RATG/Rituxan/Velcade
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.
Drug: Rabbit Antithymocyte Globulin · Drug: Velcade · Drug: Rituxan

Interventions

DrugRabbit Antithymocyte Globulin
rATG will be given 1.5mg/kg intravenous (IV) per dose.
Also known as: Thymoglobulin, rATG
DrugVelcade
Velcade will be given 1.3mg/m2 via intravenous push (IVP) per dose.
Also known as: bortezomib
DrugRituxan
Given via IV per group assignment.
Also known as: Rituximab

What researchers measure

Primary outcomes

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)
Time frame: 6 months

Secondary outcomes

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+
Time frame: 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)
Time frame: 6 months
Patient Survival at 12 Months
Patient was still alive 12 months post study enrollment.
Time frame: 12 months
Patient Allograft Survival at 12 Months
Patient's allograft was still functioning at 12 months post study enrollment
Time frame: 12 months

Results

Posted Jan 20, 2016

Participant flow

Participant flow — Overall Study
Milestone	Rabbit Antithymocyte Globulin (rATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
Started	10	10	10	10
Completed	10	10	9	8
Not completed	0	0	1	2

Outcome measures

PrimaryIncidence 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)

Time frame:: 6 months
Reported as:: Number · participants

Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection
participants	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
Incidence of Acute Rejection (Banff '97) or Antibody Mediated Rejection	2	0	5	3

SecondaryAntibody-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+

Time frame:: 6 months
Reported as:: Number · participants

Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)
participants	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
Antibody-mediated Rejection by Banff '97 Criteria (Updated 2005)	1	0	3	1

SecondaryAcute 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)

Time frame:: 6 months
Reported as:: Number · participants

Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)
participants	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
Acute Cellular Rejection by Banff '97 Criteria (Updated 2005)	1	0	1	0

SecondaryPatient Survival at 12 Months

Patient was still alive 12 months post study enrollment.

Time frame:: 12 months
Reported as:: Number · participants

Patient Survival at 12 Months
participants	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
Patient Survival at 12 Months	10	10	10	9

SecondaryPatient Allograft Survival at 12 Months

Patient's allograft was still functioning at 12 months post study enrollment

Time frame:: 12 months
Reported as:: Number · participants

Patient Allograft Survival at 12 Months
participants	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
Patient Allograft Survival at 12 Months	10	10	9	9

Adverse events

Collected over 12 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Rabbit Antithymocyte Globulin (RATG)	—	2/10 (20%)	10/10 (100%)
RATG/Rituxan	—	4/10 (40%)	10/10 (100%)
RATG/Velcade	—	4/10 (40%)	10/10 (100%)
RATG/Rituxan/Velcade	—	2/10 (20%)	10/10 (100%)

Most frequent serious events

Most frequent serious events
Event	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
CMV ViremiaInfections and infestations	1/10	3/10	4/10	2/10
Other InfectionsInfections and infestations	2/10	4/10	4/10	0/10
BKV ViremiaInfections and infestations	0/10	2/10	3/10	2/10
CMV Invasive DiseaseInfections and infestations	0/10	0/10	1/10	2/10
CMV +/- StatusInfections and infestations	1/10	0/10	0/10	1/10
EBV ViremiaInfections and infestations	0/10	0/10	1/10	0/10
BKV NephropathyInfections and infestations	0/10	1/10	1/10	0/10
EBV +/- StatusInfections and infestations	0/10	0/10	0/10	0/10
EBV-related disease / PTLDInfections and infestations	0/10	0/10	0/10	0/10

Most frequent other events

Most frequent other events
Event	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade
CTCAE Grade 1 Nausea/VomitingGastrointestinal disorders	3/10	6/10	2/10	3/10
CTCAE Grade 1 DiarrheaGastrointestinal disorders	2/10	3/10	3/10	5/10
CTCAE Grade 2 Nausea/VomitingGastrointestinal disorders	0/10	0/10	3/10	3/10
CTCAE Grade 3 Nausea/VomitingGastrointestinal disorders	3/10	1/10	1/10	1/10
CTCAE Grade 2 DiarrheaGastrointestinal disorders	2/10	3/10	3/10	3/10
CTCAE Grade 3 DiarrheaGastrointestinal disorders	0/10	1/10	2/10	1/10

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade	Total
Mean	49.9 (46.3 to 53.8)	52.8 (45.6 to 62.7)	50.6 (34.5 to 63.3)	50.1 (45.3 to 56.9)	50.9 (34.5 to 63.3)

Sex: Female, Male
Sex: Female, Male(Participants)	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade	Total
Female	5	5	8	4	22
Male	5	5	2	6	18

Region of Enrollment
Region of Enrollment(participants)	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade	Total
United States	10	10	10	10	40

Pre-transplant diabetes mellitus
Pre-transplant diabetes mellitus(participants)	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade	Total
Number	1	4	3	1	9

Dialysis pre-transplant
Dialysis pre-transplant(participants)	Rabbit Antithymocyte Globulin (RATG)	RATG/Rituxan	RATG/Velcade	RATG/Rituxan/Velcade	Total
Number	9	7	8	10	34

Study locations

2 sites

The Christ Hospital
Cincinnati, Ohio 45202, United States
The University Hospital
Cincinnati, Ohio 45219, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jan 20, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00782821
Lead sponsor: University of Cincinnati
Collaborators: Millennium Pharmaceuticals, Inc., Genzyme, a Sanofi Company
Responsible party: E. Steve Woodle (MD, FACS, University of Cincinnati) — Principal investigator
First posted: Oct 31, 2008
Start date: Sep 2008
Primary completion: Feb 2013
Completion: Mar 2013
Results posted: Jan 20, 2016
Last update: Jan 20, 2016

Study contacts

E. Steve Woodle, MD

principal investigator · University of Cincinnati

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2015. You cannot join it, but the record below documents what was studied.

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