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Using Donor Stem Cells and Alemtuzumab to Prevent Organ Rejection in Kidney Transplant Patients

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ClinicalTrials.gov Identifier: NCT00183248
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : June 21, 2012
Last Update Posted : October 2, 2012
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
George W. Burke, National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Kidney Transplantation
Kidney Disease
Kidney Failure
Interventions Drug: Alemtuzumab
Drug: Mycophenolate mofetil
Drug: Sirolimus
Drug: Tacrolimus
Procedure: Donor bone marrow stem cell infusion
Procedure: Kidney transplant
Enrollment 9
Recruitment Details One center in the United States enrolled nine subjects who were recipients of living-related (1-haplotype-matched) donor kidney transplants between September 2004 and November 2006.
Pre-assignment Details Participants underwent procedures at screening to establish inclusion/exclusion criteria.
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled ‘Detailed Description’ for additional treatment information. Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled ‘Detailed Description’ for additional treatment information.
Period Title: Overall Study
Started 4 5
Completed 3 4
Not Completed 1 1
Reason Not Completed
Lost to Follow-up             0             1
Focal glomerulosclerosis proteinuria             1             0
Arm/Group Title DBMCs Control Group Total
Hide Arm/Group Description Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled ‘Detailed Description’ for additional treatment information. Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled ‘Detailed Description’ for additional treatment information. Total of all reporting groups
Overall Number of Baseline Participants 4 5 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 9 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
 100.0%
5
 100.0%
9
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 5 participants 9 participants
41.0  (12.0) 41.8  (7.9) 41.4  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 5 participants 9 participants
Female
2
  50.0%
0
   0.0%
2
  22.2%
Male
2
  50.0%
5
 100.0%
7
  77.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 5 participants 9 participants
4 5 9
1.Primary Outcome
Title Overall Participant Survival at One Year Post Kidney Transplant
Hide Description [Not Specified]
Time Frame One year post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 4 5
Measure Type: Number
Unit of Measure: participants
4 5
2.Primary Outcome
Title Overall Kidney Graft Survival at One Year Post-Transplant
Hide Description

Number of participants that did not experience kidney graft failure[1] at one year post-transplant

[1]Graft failure is defined as the institution of chronic dialysis (at least 6 consecutive weeks, excluding participants with delayed graft function), transplant nephrectomy, or retransplantation.

Time Frame One year post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 4 5
Measure Type: Number
Unit of Measure: participants
4 5
3.Secondary Outcome
Title Participant Survival at Three Years Post Kidney Transplant
Hide Description [Not Specified]
Time Frame Three years post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 4 5
Measure Type: Number
Unit of Measure: participants
4 5
4.Secondary Outcome
Title Graft Survival at Three Years Post-Transplant
Hide Description

Number of participants that did not experience kidney graft failure[1] at three years post-transplant

[1]Graft failure is defined as the institution of chronic dialysis (at least 6 consecutive weeks, excluding participants with delayed graft function), transplant nephrectomy, or retransplantation.

Time Frame Three years post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 4 5
Measure Type: Number
Unit of Measure: participants
4 5
5.Secondary Outcome
Title Number of Kidney Biopsy-proven Acute Rejection
Hide Description

Biopsy-proven acute renal (kidney) rejection[1,2].

  1. Diagnosis of acute rejection was made by renal biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater, with higher scores indicating more severe rejection[2]
  2. Ref: Racusen LC et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999
Time Frame Three years post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who experienced an acute rejection
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 1 1
Measure Type: Number
Unit of Measure: Rejection Events
1 1
6.Secondary Outcome
Title Number of Chronic Allograft Nephropathies
Hide Description

Number of chronic allograft nephropathies[1,2,3] at 3 years post kidney transplant.

  1. Chronic allograft nephropathy is defined as renal biopsies with Banff 97 Grade I or greater[2] with higher numeric scores indicating more severe nephropathy
  2. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification[3]
  3. Reference: Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int, 55: 713-723, 1999
Time Frame Three years post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who experienced nephropathies
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 4 1
Measure Type: Number
Unit of Measure: Nephropathy Events
6 2
7.Secondary Outcome
Title Number of Graft-versus-host Disease (GVHD) Events
Hide Description A disease caused when cells from a donated stem cell graft attack the normal tissue of the transplant patient. Symptoms include jaundice, skin rash or blisters, a dry mouth, or dry eyes. Also called graft-versus-host disease.
Time Frame Three years post kidney transplant
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description:
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with Alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled 'Detailed Description' for additional treatment information.
Overall Number of Participants Analyzed 4 5
Measure Type: Number
Unit of Measure: GVHD Events
0 0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DBMCs Control Group
Hide Arm/Group Description Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive (CD34+ stem cell purified) Donor-specific Bone Marrow Cells (DBMCs). Induction therapy included alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled ‘Detailed Description’ for additional treatment information. Recipients of 1-haplotype human leukocyte antigen (HLA) matched living-donor related kidney transplantation were randomized to receive induction therapy with alemtuzumab and steroid-free dose maintenance immunosuppression consisting of mycophenolate mofetil, tacrolimus and sirolimus. Refer to section titled ‘Detailed Description’ for additional treatment information.
All-Cause Mortality
DBMCs Control Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
DBMCs Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      3/5 (60.00%)    
General disorders     
Chest pain  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Pyrexia  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Immune system disorders     
Kidney transplant rejection  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Infections and infestations     
Tonsillitis  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Urinary tract infection  1  2/4 (50.00%)  2 0/5 (0.00%)  0
Injury, poisoning and procedural complications     
Drug toxicity  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Post procedural haematoma  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Investigations     
Blood creatinine increased  1  3/4 (75.00%)  12 2/5 (40.00%)  2
Renal and urinary disorders     
Glomerulonephritis membranoproliferative  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Mesangioproliferative glomerulonephritis  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Nephrotic syndrome  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Vascular disorders     
Hypertension  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DBMCs Control Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      5/5 (100.00%)    
Blood and lymphatic system disorders     
Anaemia  1  3/4 (75.00%)  4 2/5 (40.00%)  2
Leukopenia  1  1/4 (25.00%)  1 1/5 (20.00%)  1
Neutropenia  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Cardiac disorders     
Palpitations  1  2/4 (50.00%)  2 0/5 (0.00%)  0
Tachycardia  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Congenital, familial and genetic disorders     
Hydrocele  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Ear and labyrinth disorders     
Ear pain  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Eye disorders     
Vision blurred  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Visual acuity reduced  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  0/4 (0.00%)  0 2/5 (40.00%)  2
Diarrhoea  1  0/4 (0.00%)  0 2/5 (40.00%)  2
Palatal oedema  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Stomatitis  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Swollen tongue  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Vomiting  1  0/4 (0.00%)  0 1/5 (20.00%)  1
General disorders     
Face oedema  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Oedema peripheral  1  3/4 (75.00%)  4 0/5 (0.00%)  0
Pain  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Pyrexia  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Infections and infestations     
Body tinea  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Fungal infection  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Gastroenteritis viral  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Herpes zoster  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Oral candidiasis  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Oral herpes  1  2/4 (50.00%)  2 0/5 (0.00%)  0
Upper respiratory tract infection  1  2/4 (50.00%)  2 2/5 (40.00%)  2
Urinary tract infection  1  3/4 (75.00%)  5 0/5 (0.00%)  0
Viral infection  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Investigations     
Blood alkaline phosphatase increased  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Blood triglycerides increased  1  0/4 (0.00%)  0 1/5 (20.00%)  3
Gamma-glutamyltransferase increased  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Hepatic enzyme increased  1  1/4 (25.00%)  1 3/5 (60.00%)  3
Platelet count decreased  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Platelet count increased  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Red blood cell count decreased  1  1/4 (25.00%)  1 0/5 (0.00%)  0
White blood cell count decreased  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Metabolism and nutrition disorders     
Fluid overload  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Hypercholesterolaemia  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Hyperglycaemia  1  1/4 (25.00%)  1 2/5 (40.00%)  3
Hyperlipidaemia  1  1/4 (25.00%)  1 1/5 (20.00%)  1
Hypertriglyceridaemia  1  0/4 (0.00%)  0 3/5 (60.00%)  4
Hyperuricaemia  1  0/4 (0.00%)  0 1/5 (20.00%)  2
Hypocalcaemia  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Hypokalaemia  1  2/4 (50.00%)  3 0/5 (0.00%)  0
Hypomagnesaemia  1  2/4 (50.00%)  2 0/5 (0.00%)  0
Hypophosphataemia  1  1/4 (25.00%)  1 1/5 (20.00%)  1
Nervous system disorders     
Burning sensation  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Headache  1  2/4 (50.00%)  2 0/5 (0.00%)  0
Psychiatric disorders     
Insomnia  1  0/4 (0.00%)  0 2/5 (40.00%)  2
Renal and urinary disorders     
Bladder spasm  1  1/4 (25.00%)  1 1/5 (20.00%)  1
Dysuria  1  1/4 (25.00%)  1 1/5 (20.00%)  1
Glycosuria  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Haematuria  1  1/4 (25.00%)  1 1/5 (20.00%)  1
Pollakiuria  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Proteinuria  1  3/4 (75.00%)  4 2/5 (40.00%)  3
Reproductive system and breast disorders     
Menorrhagia  1  1/4 (25.00%)  3 0/5 (0.00%)  0
Ovarian cyst  1  2/4 (50.00%)  2 0/5 (0.00%)  0
Testicular pain  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Bronchospasm  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Cough  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Dyspnoea  1  2/4 (50.00%)  2 1/5 (20.00%)  1
Oropharyngeal discomfort  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Oropharyngeal pain  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Pulmonary oedema  1  0/4 (0.00%)  0 1/5 (20.00%)  1
Tonsillar ulcer  1  1/4 (25.00%)  1 0/5 (0.00%)  0
Skin and subcutaneous tissue disorders     
Acne  1  3/4 (75.00%)  3 3/5 (60.00%)  4
Rash  1  0/4 (0.00%)  0 3/5 (60.00%)  3
Urticaria  1  2/4 (50.00%)  2 1/5 (20.00%)  2
Vascular disorders     
Hypertension  1  2/4 (50.00%)  3 4/5 (80.00%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
In July 2007 after the trial had been enrolling for approximately 42 months, enrollment was stopped at the current number of nine subjects due to time and resource constraints.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: George W. Burke III, M.D.
Organization: University of Miami
Phone: (305) 355-5060
Responsible Party: George W. Burke, National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00183248     History of Changes
Other Study ID Numbers: DAIT ITN022ST
First Submitted: September 11, 2005
First Posted: September 16, 2005
Results First Submitted: April 5, 2012
Results First Posted: June 21, 2012
Last Update Posted: October 2, 2012