Study of Combined Kidney and Blood Stem Cell Transplant From a Brother or Sister Donor (OneLegacy)
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|ClinicalTrials.gov Identifier: NCT03707262|
Recruitment Status : Recruiting
First Posted : October 16, 2018
Last Update Posted : April 13, 2022
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The purpose of this study is to find out if an investigational treatment will allow kidney transplant recipients to better accept their new kidney and stop immunosuppressive medicines. This study is for kidney transplant recipients who receive a kidney from a sibling donor.
The investigational treatment is started after kidney transplant. It begins with a regimen of a drug called rabbit anti-thymocyte globulin (rATG) combined with radiation therapy (known as total lymphoid irradiation, or TLI) to the lymph nodes and spleen. This is followed by an infusion of blood stem cells, which will be donated by the same sibling who donated their kidney. Researchers think that this treatment allows immune cells from the donor and recipient to live side by side, a condition referred to as "mixed chimerism." Mixed chimerism may help create a state of "tolerance" in kidney transplant recipients in which all immunosuppressive medications can be stopped without rejection of the transplanted kidney.
This study will test whether (1) the investigational treatment will allow patients to stop immunosuppressive medications after their kidney transplant and (2) if the treatment impacts the rate of kidney rejection and the side effects of immunosuppressive medications.
|Condition or disease||Intervention/treatment||Phase|
|Renal Transplant Rejection Tolerance Kidney Transplant||Biological: Donor CD34+ and CD3+ cells||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Donor Chimerism and Graft Survival Following Combined HLA-Identical Sibling Living Donor Kidney and Hematopoietic Stem Cell Transplantation Utilizing a Conditioning Regimen of Total Lymphoid Irradiation and Rabbit Anti-Thymocyte Globulin|
|Actual Study Start Date :||November 6, 2019|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2025|
Experimental: Donor CD34+ and CD3+ cell infusion
The investigational products are (1) an intravenous infusion of granulocyte colony-stimulating factor (GCSF)-mobilized, Miltenyi-enriched CD34+ cells (≥ 5 million cells per kilogram) followed by (2) an infusion of CD3+ cells (5 million cells per kilogram) from an HLA-identical sibling living donor.
The cells are infused around Day 11 post-transplant after the following pre-conditioning regimen:
Biological: Donor CD34+ and CD3+ cells
Infusion of GCSF-mobilized, Miltenyi-enriched CD34+ hematopoietic stem/progenitor cells (HSPCs) (≥ 5 million cells/kg) and CD3+ cells (5 million cells/kg) from an HLA-identical sibling living donor, following pre-conditioning regimen of rATG and TLI.
- Withdrawal from immunosuppressive drugs [ Time Frame: 12 months post-kidney transplant ]Percentage of subjects free from all immunosuppressive drugs at 12 months after kidney transplantation.
- Graft rejection [ Time Frame: 48 months post-kidney transplant ]Percentage of patients with graft rejection within 48 months post-transplant defined as (1) meets Banff criteria for rejection either on protocol biopsy or biopsy performed to confirm clinical suspicion of rejection or (2) clinical suspicion of rejection demonstrating response to corticosteroids in absence of biopsy when confirmatory biopsy contraindicated or declined.
- Time to graft rejection [ Time Frame: 48 months post-kidney transplant ]Time to graft rejection
- Graft failure [ Time Frame: 48 months post-kidney transplant ]Percentage of patients with graft failure as determined by return to dialysis and/or re-transplantation.
- Time to graft failure [ Time Frame: 48 months post-kidney transplant ]Time to graft failure
- Survival [ Time Frame: 12, 24, 36, and 48 months post-kidney transplant ]Percentage of subjects alive at 12, 24, 36, and 48 months post-kidney transplant
- Time to death [ Time Frame: 48 months post-kidney transplant ]Time to death (months post-transplant)
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
Recipient Inclusion Criteria:
- Males and females ages 18 years and older receiving living donor kidney transplant from an HLA-identical sibling at University of California Los Angeles (UCLA) Medical Center.
- Agrees to participate in the study and is able to give informed consent.
- Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first six months of the trial.
- Meets institutional criteria for kidney and hematopoietic stem cell transplant.
- No known contraindication to administration of rATG or radiation.
- If the patient is a female of reproductive potential (i.e., no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status) patient must be confirmed not pregnant by a serum or urine pregnancy test and must agree to practice a reliable form of contraception including hormonal treatments, barrier methods or intrauterine device for at least 12 months post-transplant.
- Karnofsky Performance Score ≥ 70.
- Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
- Adequate pulmonary function defined as forced vital capacity (FVC) and DLCO (diffusing capacity of lung for carbon monoxide) of greater than or equal to 50% of predicted.
- Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.0 times the upper limit of normal.
- Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker.
Recipient Exclusion Criteria:
- Donor is identical twin
- ABO incompatibility with donor.
- . Previous solid organ transplant.
- Multi-organ transplantation
- Previous treatment with rATG or a known allergy to rabbit proteins.
- History of active malignancy within the past 5 years with the exception of non-melanomatous skin cancer.
- Pregnant (confirmed by a serum or urine pregnancy test) or lactating.
- Leukopenia (with a white blood cell count < 3,000/ µL) or thrombocytopenia (with a platelet count < 100,000/ µL).
- Epstein Barr Virus (EBV) seronegative recipients receiving a kidney transplant from an EBV seropositive donor.
- Calculated panel reactive antibodies (cPRA) ≥ 80%.
- Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C).
- Seropositivity for HIV 1, HIV2, HTLV I, HTLV II, or West Nile Virus.
- Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis).
- Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis.
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
- Active extra-renal autoimmune disease requiring immunosuppression.
- Neuropsychiatric illness that precludes the ability to give informed consent and/or places the patient as high risk for non-compliance with the safety monitoring requirements of the study.
- Current or active abuse of alcohol and/or drugs within last 6 months.
- May not have received other immunosuppressive medications, including but not limited to alemtuzumab, belatacept, sirlolimus, everolimus, azathioprine, basiliximab, and eculizumab within one year of the study treatment
- May not have received immunotherapy drugs such as immune checkpoint inhibitors (e.g. pembrolizumab, nivolumab, and ipilimumab), tumor necrosis factor inhibitors, rituximab, and interleukin-2 within 1 year of the study treatment.
- BMI 40 or greater.
Donor Inclusion Criteria:
- HLA-identical sibling on high-resolution HLA typing who is ≥18 years of age.
- Meets institutional criteria for living kidney and allogeneic hematopoietic stem cell transplant donation.
- Medically fit to tolerate peripheral blood apheresis, including weighing ≥110 pounds, hematocrit ≥ 38%, and platelets ≥110,000/µL.
- Normal hematology, serum chemistry, and coagulation studies; or, if abnormal, the differences are not considered clinically significant.
Donor Exclusion Criteria:
- Recipient is identical twein
- ABO incompatibility with recipient.
- Medically unfit to tolerate peripheral blood apheresis (small body size, poor vascular access, etc.).
- Pregnant (confirmed by urine or serum pregnancy test) or lactating.
- Seropositivity for HIV 1, HIV2, HTLVI, HTLV II, or West Nile Virus. EBV positive donors will not be excluded unless patient is EBV negative.
- Active bacterial, fungal, mycobacterial, or viral infection (including active hepatitis B and/or C)
- Psychiatric, addictive, neurological, or other disorder that compromises ability to give true informed consent for participation in this study
- History of malignant disease other than non-melanoma skin malignancies within the last 5 years.
- No current or recent use of oral anti-coagulants. (For the purpose of this study, recent is defined as less than 60 days prior to apheresis.). Note: Use of aspirin and non-steroidal anti-inflammatory drugs, for pain and inflammation management purposes, are permitted to enroll in the study, but these drugs must be stopped 14 days prior to apheresis, however subjects who are taking aspirin for its anti-platelet/anti-thrombotic effect, are excluded.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03707262
|Contact: Dana Levin||(310) email@example.com|
|United States, California|
|University of California, Los Angeles||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Dana Levin, MPH 310-794-8893 DLevin@mednet.ucla.edu|
|Contact: Jenny Lester, MPH 310-794-9728 firstname.lastname@example.org|
|Principal Investigator: Jeffrey Veale, MD|
|Principal Investigator:||Jeffrey Veale, MD||University of California, Los Angeles|
|Responsible Party:||Jeffrey Veale, MD, Professor, David Geffen School of Medicine, University of California, Los Angeles|
|Other Study ID Numbers:||
|First Posted:||October 16, 2018 Key Record Dates|
|Last Update Posted:||April 13, 2022|
|Last Verified:||April 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Undecided|
|Plan Description:||N/A, undecided|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|