Using Donor Stem Cells and Alemtuzumab to Prevent Organ Rejection in Kidney Transplant Patients
Pilot Study Using Donor Stem Cells and Campath-1H to Induce Renal Transplant Tolerance (ITN022ST)
調査の概要
状態
詳細な説明
Organ transplantation is a common procedure in hospitals, but organ rejection and serious side effects are potential problems for the patient. Mycophenolate mofetil, sirolimus, and tacrolimus are drugs used to decrease immune system activity in people who have received organ transplants so that the new organ will not be rejected. Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients. In this study, alemtuzumab will be used to destroy the recipient's white blood cells (WBCs) at the time of transplantation. It is hoped that WBCs produced after alemtuzumab administration will recognize the transplanted liver as "self" and will not attack the new kidney.
To further assist the immune system in accepting the donor kidney, some patients in this study will also receive two infusions of bone marrow stem cells from the kidney donor. Bone marrow stem cells are adult blood cells from which other specialized blood cells, such as T cells, develop. Treatment with these cells is believed to create a state of "chimerism" in the body, where the immune cells of both the donor and recipient can coexist and tolerate the presence of a donor organ. This study will evaluate the safety and effectiveness of an antirejection regimen including alemtuzumab and other immunosuppressive medications and donor bone marrow stem cell infusions in patients undergoing kidney transplantation.
This study will last 3 years. Participants will be randomly assigned to receive either the full immunosuppressive therapy and donor bone marrow stem cell infusions (Group 1) or immunosuppressive therapy alone (Group 2). Patients will undergo kidney transplantation at the start of the study on Day 0. Patients will receive inpatient infusions of alemtuzumab on Days 0 and 4. Starting on Day 0, patients will begin taking mycophenolate mofetil; starting on Day 1, patients will also begin taking tacrolimus. On Day 5, patients in Group 1 will receive their first of 2 infusions of purified stem cells taken from the kidney donor's bone marrow; their second infusion of stem cells will occur sometime between Months 4 and 6 post-transplant.
Beginning between Months 4 and 6 post-transplant, all participants will begin receiving low-dose maintenance immunosuppressive therapy with sirolimus, as is typical for post-transplant antirejection therapy. One year post-transplant, patients will be evaluated for the potential to withdraw some or all of this maintenance immunotherapy. Participants will be monitored for 3 years post-transplant. Urine collection will occur at Week 1 and Months 1, 3, 6, and 9. At Months 12, 24, and 30, participants will undergo kidney biopsies. Blood collection will occur at regular intervals for laboratory tests to evaluate the immune system's response to the transplanted kidney.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
-
-
Florida
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Miami、Florida、アメリカ、33136
- University of Miami
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Weight greater than 40 kg (88.2 lbs)
- Will be receiving a living-related (1-haplotype-matched donor/recipient) primary kidney allograft
- Negative B-cell and T-cell cytotoxic and flow cytometry crossmatch (1-haplotype-matched donor/recipient pairs with a minimum of 1 HLA DR 1A and 1B locus in common and panel-reactive antibodies [PRA] of less than 10%)
- Normal echocardiogram (ECG) with an ejection fraction of greater than 50%
- Received full course of vaccination for hepatitis B virus (HBV), completed at least 6 weeks before transplantation, OR has naturally acquired immunity
- Willing to comply with the study visits
- Willing to use acceptable forms of contraception
Exclusion Criteria:
- Previously received or is receiving an organ transplant other than a kidney
- Receiving an ABO (blood type) incompatible donor kidney
- Human Immunodeficiency Virus (HIV) infected
- Antibody positive for hepatitis C virus (HCV)
- Surface antigen positive for hepatitis B virus (HBV)
- Recipient or donor is positive for tuberculosis (TB), under treatment for suspected TB, or previously exposed to TB (positive Mantoux test)
- Current cancer or a history of cancer within the 5 years prior to study entry. Patients who have had successfully treated nonmetastatic basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix are not excluded.
- Significant liver disease, defined as having continuously elevated aspartate aminotransferase (AST SGOT) or alanine aminotransferase (ALT SGPT) levels greater than 3 times the upper value of the normal range within 28 days prior to study entry
- Uncontrolled concomitant infections, severe diarrhea, vomiting, active upper gastrointestinal tract malabsorption, active peptic ulcer, or any other unstable medical condition that could interfere with this study
- Currently receiving an investigational drug or received an investigational drug within 30 days prior to transplant
- Currently receiving any immunosuppressive agent
- Anticipated contraindication to taking medications orally or via nasogastric tube by the morning of Day 2 following completion of the transplant procedure
- Require certain medications
- Known hypersensitivity to any of the study medications, thymoglobulin daclizumab, or corticosteroids
- Certain screening laboratory values. More information on this criterion can be found in the protocol.
- Any form of substance abuse, psychiatric disorder, or other condition that, in opinion of the investigator, may interfere with the study
- Anticipated contraindication to tacrolimus administration for longer than 5 days post-transplant
- Currently undergoing peritoneal dialysis
- PRA value less than 10% at any time prior to study entry
- Graves disease. Patients with Graves disease adequately treated with radioiodine ablative therapy are not excluded.
- Cytomegalovirus (CMV) or Epstein-Barr virus (EBV) negative kidney recipient receiving a kidney from a CMV or EBV positive donor
- Pregnancy or breastfeeding
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：DBMCs
Kidney transplantation, followed by immunotherapy given along with kidney donor Donor bone Bone marrow Marrow stem cell Cells (DBMCs) infusions
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Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
他の名前：
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
他の名前：
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
他の名前：
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
他の名前：
2 doses of kidney donor's bone marrow stem cells by IV infusion on Day 5 and sometime between Months 4 and 6
Occurs at study entry
|
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アクティブコンパレータ：Control Group
Kidney transplantation, followed by immunotherapy
|
Immunosuppressant; 2 doses of drug by intravenous (IV) infusion on Days 0 and 4
他の名前：
Immunosuppressant; oral daily dose starting Day 0 until withdrawal or end of the study
他の名前：
Immunosuppressant; oral daily dose starting between Months 4 and 6 post-transplant until withdrawal or end of the study
他の名前：
Immunosuppressant; daily dose starting Day 1 until withdrawal or end of the study
他の名前：
Occurs at study entry
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall Participant Survival at One Year Post Kidney Transplant
時間枠：One year post kidney transplant
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One year post kidney transplant
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Overall Kidney Graft Survival at One Year Post-Transplant
時間枠：One year post kidney transplant
|
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. |
One year post kidney transplant
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Participant Survival at Three Years Post Kidney Transplant
時間枠：Three years post kidney transplant
|
Three years post kidney transplant
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|
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Graft Survival at Three Years Post-Transplant
時間枠：Three years post kidney transplant
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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. |
Three years post kidney transplant
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Number of Kidney Biopsy-proven Acute Rejection
時間枠：Three years post kidney transplant
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Biopsy-proven acute renal (kidney) rejection[1,2].
|
Three years post kidney transplant
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Number of Chronic Allograft Nephropathies
時間枠：Three years post kidney transplant
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Number of chronic allograft nephropathies[1,2,3] at 3 years post kidney transplant.
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Three years post kidney transplant
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Number of Graft-versus-host Disease (GVHD) Events
時間枠：Three years post kidney transplant
|
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.
|
Three years post kidney transplant
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：George W. Burke, III, MD、University of Miami
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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