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Trial record 37 of 498 for:    stem cell kidney

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 : Not yet recruiting
First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Collaborator:
OneLegacy Foundation
Information provided by (Responsible Party):
Jeffrey Veale, MD, University of California, Los Angeles

Brief Summary:

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

Detailed Description:
In spite of the pronounced benefit of kidney transplantation in prolonging survival and improving the quality of life of patients with end stage renal disease, it is still hampered by the risk of graft rejection and the need for lifelong immunosuppression. Researchers have sought to circumvent these challenges through the use of combined kidney and hematopoietic stem cell transplantation to induce immune tolerance. This study will build upon published reports showing favorable results for the TLI/rATG regimen in HLA-matched living donor transplant recipients. The investigators seek to confirm that patients treated with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG) followed by human leukocyte antigen (HLA)-identical donor hematopoietic progenitor cell transplant can be withdrawn from immunosuppressive drugs while maintaining normal renal function after renal transplantation. At serial time points, (1) graft function will be monitored, (2) chimerism will be measured in recipient white blood cell subsets, and (3) protocol biopsies of the graft will be obtained. An attempt will be made to discontinue tacrolimus at 12 months if the following conditions are met: (1) chimerism (defined as ≥5% donor type cells among the T cells, B cells, NK cells, and granulocytes) is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) stable graft function without clinical rejection episodes is maintained, (3) there is lack of histologic rejection on protocol biopsies, and (4) there is no evidence of graft vs. host disease (GVHD). Recipients in the proposed study will be given a target dose of ≥ 5 x106 CD34+ cells/kg and 5x106 CD3+ cells/kg with the goal of achieving durable mixed chimerism.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : February 25, 2019
Estimated Primary Completion Date : February 25, 2022
Estimated Study Completion Date : February 25, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Donor CD34+ and CD3+ cell infusion

The investigational products are (1) an intravenous infusion of 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:

  1. 5 doses of rATG (1.5 mg/kg IV per day for 5 days, starting on the day of transplant)
  2. 10 doses of TLI (120 cGY x 10 fractions, starting the day after transplant)
Biological: Donor CD34+ and CD3+ cells
Infusion of GCSF-mobilized, Miltenyi-enriched CD34+ 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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Time to graft rejection [ Time Frame: 48 months post-kidney transplant ]
    Time to graft rejection

  3. 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.

  4. Time to graft failure [ Time Frame: 48 months post-kidney transplant ]
    Time to graft failure

  5. 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

  6. 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
Criteria

Recipient Inclusion 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 six months of the trial.
  4. Meets institutional criteria for kidney and hematopoietic stem cell transplant.
  5. No known contraindication to administration of rATG or radiation.
  6. If of reproductive potential, agrees to practice a reliable form of contraception - including hormonal treatments, barrier methods, or intrauterine device - for at least 12 months post-transplant.
  7. Karnofsky Performance Score ≥ 70.
  8. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
  9. Adequate pulmonary function defined as FVC and DLCO of greater than or equal to 50% of predicted.
  10. 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.
  11. Adequate social support based on evaluation by the UCLA renal transplant team licensed clinical social worker.

Recipient Exclusion Criteria:

  1. ABO incompatibility with donor.
  2. Previous treatment with rATG or a known allergy to rabbit proteins.
  3. History of active malignancy within the past 5 years with the exception of non-melanomatous skin cancer.
  4. Pregnant women or nursing mothers.
  5. Leukopenia (with a white blood cell count < 3,000/ µL) or thrombocytopenia (with a platelet count < 100,000/ µL).
  6. EBV seronegative recipients receiving a kidney transplant from an EBV seropositive donor.
  7. cPRA ≥ 80%.
  8. Active bacterial, fungal, mycobacterial or viral infection.
  9. Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis.
  10. Seropositivity for HIV or HTLV-1 or 2.
  11. Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis).
  12. 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.
  13. 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.
  14. Current or active abuse of alcohol and/or drugs within last 6 months.
  15. BMI 40 or greater.

Donor Inclusion Criteria:

  1. HLA-identical sibling on high-resolution HLA typing who is ≥18 years of age.
  2. Meets institutional criteria for living kidney and allogeneic hematopoietic stem cell transplant donation.
  3. Medically fit to tolerate peripheral blood apheresis, including weighing ≥110 pounds, hematocrit ≥ 38%, and platelets ≥110,000/µL.
  4. Normal hematology, serum chemistry, and coagulation studies; or, if abnormal, the differences are not considered clinically significant.

Donor Exclusion Criteria:

  1. ABO incompatibility with recipient.
  2. Medically unfit to tolerate peripheral blood apheresis (small body size, poor vascular access, etc.).
  3. Pregnant (confirmed by urine or serum pregnancy test) or lactating.
  4. Positive for HIV 1, HIV 2, HTLV I, HTLV II, or West Nile Virus. EBV positive donors will not be excluded unless patient is EBV negative.
  5. Active hepatitis B and/or C.
  6. Psychiatric, addictive, neurological, or other disorder that compromises ability to give true informed consent for participation in this study
  7. History of malignant disease other than non-melanoma skin malignancies within the last 5 years.
  8. Taking medications that would interfere with apheresis, including aspirin, coumadin, or steroids.
  9. Inadequate peripheral venous access to allow apheresis and not a suitable candidate for placement of a central catheter.

Information from the National Library of Medicine

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


Contacts
Contact: Meg Bradley (310) 794-3452 mabradley@mednet.ucla.edu

Sponsors and Collaborators
Jeffrey Veale, MD
OneLegacy Foundation
Investigators
Principal Investigator: Jeffrey Veale, MD University of California, Los Angeles

Responsible Party: Jeffrey Veale, MD, Associate Professor, David Geffen School of Medicine, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT03707262     History of Changes
Other Study ID Numbers: OneLegacy Foundation
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
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

Keywords provided by Jeffrey Veale, MD, University of California, Los Angeles:
Tolerance
Kidney Transplant

Additional relevant MeSH terms:
Thymoglobulin
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents