Clinical trial NCT00801632: Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection
Official title: Renal Allograft Tolerance Through Mixed Chimerism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplantation
Kidney Failure, Chronic
Keywords: renal allograft tolerance
mixed chimerism
kidney transplant
bone marrow transplant
antirejection
immunosuppression
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2008-12-03
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.

Detailed description: All patients receiving an organ or tissue transplant must take special medicines known as "immunosuppressive drugs" in order to prevent the immune system from rejecting the transplant. These drugs can be very effective, but they leave the patient at an increased risk of serious infections and certain types of cancer. New methods of preventing transplant rejection are needed.

Researchers have found that transplanting both bone marrow and a kidney from the same donor can create what is called "mixed chimerism." This means that the transplant recipient has a mixture of the donor and recipient's immune systems. It is believed that this mixture of immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This clinical trial will study more patients to confirm if the technique is safe and effective.

Patients eligible for this study must be candidates for a living kidney transplant, and have an eligible donor identified. The transplant recipient and donor must both consent to participate in this study. Transplant recipients enrolled in the study will receive both kidney and bone marrow transplants from the same living donor. Prior to the transplant procedure, the transplant recipient will undergo a "conditioning regimen" that prepares their immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. After the transplant procedure, transplant recipients will be prescribed steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and kidney function meet certain criteria.

Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the transplant procedure. After the transplant, patients will remain in the hospital until the doctor feels they are well enough to go home. Recipients will receive approximately monthly checkups over a period of 2 years after transplant, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5 years after transplant. Checkups will include physical exams, and blood and urine tests to assess immune system and kidney function. At four of these checkups, a kidney biopsy will be requested.

Transplant donors enrolled in the study will attend a screening visit, which will include a physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant donors may be asked at a later date to donate additional blood samples for research purposes.

Eligibility criteria: Inclusion Criteria:

* Awaiting first or second transplant with a living donor or first transplant with a cadaveric donor
* For living-donor transplants, must have one or more HLA antigen-mismatched donors identified
* Serologic evidence of prior exposure to Epstein-Barr virus (EBV)

Exclusion Criteria:

* ABO blood group-incompatibility for a kidney graft of tissue from a donor
* Decreased circulating white blood cell count
* Positive for HIV-1, hepatitis B and C viruses
* Have had prior radiation therapy that could limit dose
* Lung capacity \<50% of predicted normal
* Evidence of insufficient cardiac capacity
* Unwilling to use adequate contraception until 2 years after transplant
* Lactation or pregnancy
* Presence of antibody against the donor

Primary outcomes:
measure: Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks
timeFrame: 48 months post-transplant
Secondary outcomes:
measure: Percentage of Participants Experiencing Acute Rejection
timeFrame: Transplantation until study completion or participant termination (up to five years)
measure: Change in Renal Function
timeFrame: Transplantation until study completion or participant termination (up to five years)
measure: Percentage of Participants With Graft Survival Through 156 Weeks
timeFrame: Transplantation until week 156
measure: Percentage of Participants Surviving Through 156 Weeks
timeFrame: Transplantation until week 156
measure: Time to Neutrophil Recovery Following Transplant
timeFrame: Transplantation until study completion or participant termination (participants followed up to five years)
measure: Time to Platelet Recovery Following Transplant
timeFrame: Transplantation until study completion or participant termination (participants followed up to five years)
measure: Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection
timeFrame: Transplantation until study completion or participant termination (participants followed up to five years)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massacusetts General Hospital
name: David Sachs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Ben Cosimi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.
citation: Kawai T, Sachs DH, Sykes M, Cosimi AB; Immune Tolerance Network. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med. 2013 May 9;368(19):1850-2. doi: 10.1056/NEJMc1213779. No abstract available.