RECRUITING

Study of Combined Kidney and Blood Stem Cell Transplant From a Brother or Sister Donor

Conditions

Renal Transplant Rejection Tolerance Kidney Transplant

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2019-11-06

Study Completion:2025-02

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03707262

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Males and females ages 18 years and older receiving living donor kidney transplant from an HLA-identical sibling at UCLA Medical Center. 2. Agrees to participate in the study and is able to give informed consent. 3. Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first three to six months of the trial at the physician's discretion. 4. Meets institutional criteria for kidney and HSPC transplant. 5. No known contraindication to administration of rATG or radiation. 6. If 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. 7. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram. 8. Adequate pulmonary function defined as FVC and DLCO of greater than or equal to 50% of predicted. 9. Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and AST/ALT ≤ 2.0 times the upper limit of normal. 10. Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker.	1. Donor is identical twin. 2. ABO incompatibility with donor. 3. Previous solid organ transplant 4. Multi-organ transplantation 5. Previous treatment with rATG or a known allergy to rabbit proteins 6. History of active malignancy within the past 5 years with the exception of non-melanomatous skin cancer. 7. Pregnant (confirmed by urine or serum pregnancy test) or lactating. 8. Leukopenia (with a white blood cell count \< 3,000/ µL) or thrombocytopenia (with a platelet count \< 100,000/ µL). 9. Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C). 10. Positive HLA DSA 11. Seropositivity for HIV 1, HIV 2, HTLVI, HTLV II 12. Active West Nile Virus infection 13. Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis). 14. Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis. 15. 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. 16. Active extra-renal autoimmune disease requiring immunosuppression. 17. 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. 18. May not have received other immunosuppressive medications, including but not limited to alemtuzumab, belatacept, sirlolimus, everolimus, azathioprine, basiliximab, and eculizumab within six months of the study treatment. Use of corticosteroids prescribed for a time-limited indication (\</= 4 weeks) and stopped at least 4 weeks before the kidney transplant is acceptable. 19. 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 six months of the study treatment. 20. Current or active abuse of alcohol and/or drugs within last 6 months. 21. BMI 40 or greater.

Inclusion Criteria

Exclusion Criteria

1. Males and females ages 18 years and older receiving living donor kidney transplant from an HLA-identical sibling at UCLA Medical Center.
2. Agrees to participate in the study and is able to give informed consent.
3. Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first three to six months of the trial at the physician's discretion.
4. Meets institutional criteria for kidney and HSPC transplant.
5. No known contraindication to administration of rATG or radiation.
6. If 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.
7. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
8. Adequate pulmonary function defined as FVC and DLCO of greater than or equal to 50% of predicted.
9. Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and AST/ALT ≤ 2.0 times the upper limit of normal.
10. Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker.

1. Donor is identical twin.
2. ABO incompatibility with donor.
3. Previous solid organ transplant
4. Multi-organ transplantation
5. Previous treatment with rATG or a known allergy to rabbit proteins
6. History of active malignancy within the past 5 years with the exception of non-melanomatous skin cancer.
7. Pregnant (confirmed by urine or serum pregnancy test) or lactating.
8. Leukopenia (with a white blood cell count \< 3,000/ µL) or thrombocytopenia (with a platelet count \< 100,000/ µL).
9. Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C).
10. Positive HLA DSA
11. Seropositivity for HIV 1, HIV 2, HTLVI, HTLV II
12. Active West Nile Virus infection
13. Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis).
14. Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis.
15. 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.
16. Active extra-renal autoimmune disease requiring immunosuppression.
17. 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.
18. May not have received other immunosuppressive medications, including but not limited to alemtuzumab, belatacept, sirlolimus, everolimus, azathioprine, basiliximab, and eculizumab within six months of the study treatment. Use of corticosteroids prescribed for a time-limited indication (\</= 4 weeks) and stopped at least 4 weeks before the kidney transplant is acceptable.
19. 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 six months of the study treatment.
20. Current or active abuse of alcohol and/or drugs within last 6 months.
21. BMI 40 or greater.

Contacts and Locations

Study Contact

Ruth Wynne Jones

CONTACT

424-402-9564

rwynnejones@mednet.ucla.edu

Jenny Lester

CONTACT

310-794-9728

jlester@mednet.ucla.edu

Principal Investigator

Jeffrey Veale, MD

PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Study Locations (Sites)

University of California, Los Angeles

Los Angeles, California, 90095

United States

Collaborators and Investigators

Sponsor: Jeffrey Veale, MD

Jeffrey Veale, MD, PRINCIPAL_INVESTIGATOR, University of California, Los Angeles

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-11-06

Study Completion Date2025-02

Study Record Updates

Study Start Date2019-11-06

Study Completion Date2025-02

Terms related to this study

Keywords Provided by Researchers

Tolerance
Kidney Transplant

Additional Relevant MeSH Terms

Renal Transplant Rejection
Tolerance
Kidney Transplant